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1 eterious or lethal regions of the phenotypic sequence space.
2 e-based function annotation of novel protein sequence space.
3 antly constrains the adaptive exploration of sequence space.
4 the most comprehensive datasets on tolerated sequence space.
5 nbiased, as is the vast majority of possible sequence space.
6 ed on independent data sets within a limited sequence space.
7 ith the latter being "movable" in amino acid sequence space.
8 ered DNA binding molecules across the entire sequence space.
9 s, but has limited access to vast amounts of sequence space.
10  each other to explore the maximum potential sequence space.
11 istics remain to be discovered in unexplored sequence space.
12 itro mutagenesis and samples a large protein sequence space.
13 thm for between-array normalization to probe sequence space.
14 ctional determinants within the well-defined sequence space.
15 te a previously unexplored region of protein sequence space.
16 e causes behind the observed irregularity in sequence space.
17 of understanding the dynamics of the protein sequence space.
18 e essentially infinite complexity of protein sequence space.
19 unctional DNA, RNA, and protein molecules in sequence space.
20 s understand the distribution of function in sequence space.
21 landscape, relating function to structure in sequence space.
22 er frequency across the entire span of phage sequence space.
23 r never seen in the Vibrio region of 5S rRNA sequence space.
24  a computational screen to search the entire sequence space.
25 not strong enough to offset the huge size of sequence space.
26 to achieve a rapid basic coverage of protein sequence space.
27 ncept to visualization is a multidimensional sequence space.
28 od of time without searching an enormous RNA sequence space.
29  of the genomic and consequently the protein sequence space.
30 ibution onto a two-dimensional projection of sequence space.
31 plicable and generalize to unseen regions of sequence space.
32 e essentially infinite complexity of protein sequence space.
33  from sparse sampling of a larger portion of sequence space.
34 bpopulations, which diffuse independently in sequence space.
35 s the curated selection from a combinatorial sequence space.
36 ased datasets or classify previously unknown sequence space.
37 ially adaptive processes for 'exploring' DNA sequence space.
38 ering of cleavable and uncleavable motifs in sequence space.
39 at fitness landscapes can be translocated in sequence space.
40  how frequently such regulators arise within sequence space.
41 n to chart the fitness landscapes in protein sequence space.
42 derive in vitro GR binding affinities across sequence space.
43 ominance of a single variant within a narrow sequence space.
44 s, enables high-throughput mapping of enzyme sequence space.
45 siting disordered or nonfunctional points in sequence space.
46 echanism through which HCV can explore novel sequence space.
47 ts and many targets uniformly distributed in sequence space.
48 efficiently obtain a certain coverage of the sequence-space.
49 limited multiplexing, but obscures available sequencing space.
50 leavage, thus preventing them from consuming sequencing space.
51 s challenging to generalize reliably to vast sequence spaces(4-6).
52                                          The sequence space accessed by primer extension dictates pot
53  functional enrichment in regions of protein sequence space accessible by recombination and provide a
54 his is that protein design should define the sequence space accessible to a given structure, rather t
55 imensional protein structure that affect the sequence space accessible to the evolution of HIV-1.
56                     Predictions of tolerated sequence space afforded by the model provide insights in
57 ere, we show that our procedure converges in sequence space, albeit not to the native sequence of the
58  untapped window into the history of protein sequence space, allowing events of genetic code expansio
59 at are not obvious; using motifs rather than sequence space also reduces search times considerably.
60 loring only an infinitesimal fraction of the sequence space and by their use of parametric approximat
61  patterns that completely covers the natural sequence space and can capture functional and structural
62 m the distribution of functional variants in sequence space and epistasis between residues.
63  antibody maturation within the framework of sequence space and fitness landscapes.
64 d lambda use the same strategy for searching sequence space and have almost identical patterns of div
65 nherent abundance of functional genotypes in sequence space and how accessible those genotypes are to
66 M is used to search the undiscovered peptide sequence space and identify Pareto-optimal candidates th
67 cially constructed representatives of the GA sequence space and scan the phage-displayed recombinant
68 es and capacities by expanding the encodable sequence space and simplifies the computational burden i
69 sequences, permitting greater exploration of sequence space and stable folding.
70 cture determination to explore novel protein sequence space and structure-based function annotation.
71 ses have, in recent years, been expanding in sequence space and substrate spectrum under the challeng
72 arity as an efficient strategy for searching sequence space and that the germline V gene families evo
73 culational accuracy while limiting the input sequence space and the conformations included in each pa
74 ular eukaryotes due to the larger intergenic sequence space and the increased complexity in regulatio
75               Yet, current methods merge the sequence space and the structure space into a single spa
76 uilds two separate networks to represent the sequence space and the structure space.
77  may lead to more accurate depictions of the sequence space and to applications in the discovery of n
78 cognized, yet our limited knowledge of viral sequence space and virus-host interactions precludes acc
79 re are many unstable sequences in the design sequence space and when users are satisfied with enumera
80 ten aid in the discovery of global optima in sequence space and/or lessen the number of generations i
81 g increasingly important in exploring enzyme sequence-space and creating improved or novel enzymes.
82    AMPs are versatile, have almost unlimited sequence space, and can be tuned for broad-spectrum or s
83 aying antibody diversity relative to natural sequence space, and has been shown to have diagnostic an
84 any RNA molecules sampled at random from RNA sequence space, and on 30 biological RNA molecules.
85 out the clustering of functional proteins in sequence space, and provides a basis for interpreting th
86 ons are the unfathomable vastness of protein sequence space, and the difficulty in making direct phys
87 ancestors demonstrates that large regions of sequence space are compatible with metamorphic folding.
88 to characterize alternative histories in the sequence space around an ancient transcription factor, w
89 signed sequences represent an enlargement of sequence space around native sequences.
90                 EWAK* then takes this pruned sequence space as input and, using a user-specified ener
91 tral drift screens to achieve large jumps in sequence space as may be required for the deimmunization
92 constituting catalytically versatile hubs in sequence space as potential starting points for the acqu
93 ined library diversity explores a comparable sequence space as the donor-derived natural repertoire a
94 e a new approach to explore and quantify the sequence space associated with a given protein structure
95 lysis provides a basis for understanding the sequence space associated with CaM function and should h
96                            One way to access sequence space at a higher density would be to make use
97 chive records to obtain complete coverage of sequence space at several resolutions while hiding redun
98 ion of redox potential which occurs when all sequence space available through mutation at two positio
99  Third, these nucleation points restrict the sequence space available to the protein during evolution
100 te that class II microcins encompass diverse sequence space, bacterial strains of origin, spectra of
101  with the test sequence by using a metric in sequence space based on nearest-neighbor connectivity.
102                        Clustering of protein sequence space based on sequence similarity helps organi
103 ables focusing of an scFv library in soluble sequence space before functional screening and thus can
104 h coding would have had in exploring a wider sequence space before translation became highly specific
105        Furthermore, a route through foldable sequence-space between the simple peptide motif and exta
106 y are thus not only a generic feature of RNA sequence space but are relevant for the molecular evolut
107 rojects are increasing structure coverage of sequence space but have not significantly expanded the p
108 r protein design can sample large regions of sequence space, but suffer from undersampling of conform
109 ely similar sequences to yield a covering of sequence space by a representative subset of sequences.
110                         Thus, exploration of sequence space by a viral genome (in this case an unsegm
111 rocesses to guide the search through protein sequence space by designing, constructing, and testing c
112 ese foldable sequences have been selected in sequence space by evolution.
113 d a simple method for exploring nucleic acid sequence space by nonhomologous random recombination (NR
114                                Combinatorial sequence space can be quite expensive to sample experime
115  for this particular aptamer, the functional sequence space can be represented as a rugged landscape
116  demonstrates that the functional portion of sequence space can be significantly expanded by epistasi
117 lution-guided mutagenesis and the mapping of sequence space can be used to design large sets of ortho
118 ctural clustering and motif detection in the sequence space can efficiently identify side chain motif
119 measurements of biomolecular activity across sequence space can greatly expand our understanding of R
120 ng the density of functional biomolecules in sequence space, characterizing diversity in natural popu
121 vement in affinity by maximizing sampling of sequence space close to the original selected antibody m
122 tness landscapes due to its relatively small sequence space combined with its importance in synthetic
123     These results suggest that the volume of sequence space compatible with a given protein fold is d
124            We obtain an approximation of the sequence space compatible with a protein by designing a
125 ltiple sequence alignment that describes the sequence space compatible with the structure of interest
126 ance between the sequences in the subsets of sequence space compatible with their structures.
127 sters (UniRef) speed similarity searches via sequence space compression by merging sequences that are
128 d variants provide a fast method for testing sequence space computationally.
129   Nucleic acid polymers selected from random sequence space constitute an enormous array of catalytic
130  does not access a large fraction of protein sequence space corresponding to primarily nonconservativ
131 natorial strategy for accessing nucleic acid sequence space corresponding to proteins comprising sele
132 to observe how selective pressure shapes the sequence space covered by functional molecules.
133 ations of genotypes in the joint protein-DNA sequence space defined by an historical transition in TF
134 recombination zone" describes that region of sequence space-defined by the residues that will ultimat
135  We conclude that the position of a virus in sequence space defines its mutant spectrum, evolutionary
136           We observed that the subset of the sequence space derived by using our design procedure is
137 he actual historical paths taken through RNA sequence space during 5S rRNA evolution would have most
138 sign algorithms, which aim to search a large sequence space efficiently and thus cannot rely on tempo
139  each of the GPCR classes, well separated in sequence space, enables an integrated superfamily-wide a
140 irected protein evolution and to explore the sequence space encoded by mutating multiple positions si
141 isition of function involved a large jump in sequence space enriching for truncations that removed >4
142 sive conformational sampling is coupled with sequence space exploration so that binding preferences f
143          Using synonymous alleles to enlarge sequence space exploration, we have retrieved 13 mutatio
144 y be used to quantify the characteristics of sequence space for a chosen structure without explicitly
145 ts the extent to which the model may explore sequence space for a prescribed set of parameters.
146 trate a critical expansion of the targetable sequence space for a type II-A CRISPR-associated enzyme
147 zyme superfamily requires the exploration of sequence space for adaptation to a new substrate with re
148 CS systems by allowing one to quickly search sequence space for mutations or even entirely new sequen
149 f this information would allow one to search sequence space for mutations that can be used to systema
150 uires the ability to search large volumes of sequence space for proteins with specific structural or
151 lection or screening to search vast areas of sequence space for sets of mutations that provide insigh
152 ient can significantly enlarge the available sequence space for the emergence of catalytically active
153 raries are inefficient at searching the vast sequence space for the small fraction of vectors possess
154 a fitness landscape, exploring nearly all of sequence space, for short RNAs surviving selection in vi
155 tructural domains, or by short walks through sequence space from ancestral structures.
156  is approximately 200 amino acids removed in sequence space from the catalytic nucleophile.
157 ns to the core DNA binding domain, remote in sequence space from the site of mutation.
158 lity, proteins have wide latitude to explore sequence space, generating biophysical diversity and pot
159     De novo protein design explores the full sequence space, guided by the physical principles that u
160                Recent work exploring protein sequence space has revealed a new glycoside hydrolase (G
161 ens of PAS domains across a broad section of sequence space have been solved, revealing a conserved t
162 on which 130,000 peptides chosen from random sequence space have been synthesized.
163 y-that serves as a determinant of entropy in sequence space, i.e., the ability of a protein to accept
164 hgbRNA) present in blood can occupy valuable sequencing space, impacting detection and quantification
165 lating RNA, with nearly complete coverage of sequence space in a central 21-nucleotide region.
166 from the original pool on the exploration of sequence space in a doped reselection experiment.
167 hput, limiting our ability to widely explore sequence space in a quantitative manner.
168 ccur multiple times in a local region of RNA sequence space in fact usually will be accepted in any s
169               It is shown that exploring the sequence space in the vicinity of the sequence with unkn
170 lp taxonomically identify 7-38% of 'unknown' sequence space in viromes.
171 ecies population has moved into a segment of sequence space in which the average fitness value is neu
172 nusual evolutionary strategy for sampling of sequence space in which the gene encoding an important e
173 f fitness for many mutants and even complete sequence spaces in some cases.
174 sequence information, structure information, sequence space information and structure space informati
175 mmunity resource that organizes this unknown sequence space into 27 K high confidence protein cluster
176                  By projecting the large TCR sequence space into a handful of biophysicochemical desc
177             The basic idea is to partition a sequence space into a set of subspaces using a partition
178 een optimal native structures, which divides sequence space into fast-folding, thermally stable famil
179                              Mapping protein sequence space is a difficult problem that necessitates
180       The dynamics of the population in this sequence space is consistent with an adaptive walk on an
181                                   The entire sequence space is explored by each HCV genotype and subt
182    In reality, the dimensionality of protein sequence space is higher (20(L)) and there may be higher
183                                          The sequence space is initially searched by Monte Carlo samp
184                                   The entire sequence space is interrogated simultaneously, and the a
185 ess diverse than the sequences, and that DNA sequence space is larger and more diverse than DNA struc
186                  These results indicate that sequence space is not densely occupied.
187 dy strongly supports the notion that peptide sequence space is rich in small peptides, which might be
188 lgorithm consists of an outer loop, in which sequence space is sampled by a Monte Carlo search with s
189 d that naturally occurring cyanophage genome sequence space is statistically clustered into discrete
190               Bacterial and archaeal isolate sequence space is still far from saturated, and future e
191 n and core gene sets and suggested that this sequence space is well-sampled.
192 ere we directly investigate how crowded this sequence space is, by generating novel two-component sig
193 st of the R domain has been free to drift in sequence space leading to a more star-like phylogeny tha
194 generation methods grant us access to a vast sequence space (libraries of >1012 enzyme variants) that
195 s suggests that the interdependencies in RNA sequence space may be more complex than currently apprec
196  that the heretofore neglected dimensions of sequence space may change our views on how proteins evol
197 tinct catalytic structure than 8-17 and that sequence space may contain additional examples of DNA mo
198 ersity must be focused into those regions of sequence space most likely to yield well folded structur
199 hindered fast iteration and interrogation of sequence space needed to identify new RNA devices.
200  elements with changes in the core half-site sequence, spacing nucleotide, and flanking nucleotides.
201 stigate the importance of the core half-site sequences, spacing nucleotide, flanking sequences, and o
202 opathy indexes were obtained to validate the sequence space observations using Shannon entropy and in
203 r design procedure is similar in size to the sequence spaces observed in nature.
204                             Neighborhoods in sequence space of a given radius around an RNA molecule
205 ge can be overcome by (i) sampling the large sequence space of a given scaffold through a phage displ
206 tly represented by mutations in the combined sequence space of a set of epitopes within the viral gen
207            In addition, we have explored the sequence space of all beta-trefoil proteins and have det
208          We therefore explore the functional sequence space of bnAb C05, which targets the receptor-b
209 pled by RECON MSD resembled the evolutionary sequence space of flexible proteins, particularly when c
210                           However, the large sequence space of foreign antigens presents an obstacle
211                 We systematically mapped the sequence space of four key residues in the Escherichia c
212 oteins resulted in a readily visualizable 3D sequence space of globins, where several subfamilies and
213 computational model to predict the tolerated sequence space of HIV-1 protease reachable by single mut
214 primarily, and unintentionally, screened the sequence space of microRNA seeds instead of the intended
215 is limitation, we systematically scanned the sequence space of native IDPs and designed artificial ID
216 ional, structure-based method to predict the sequence space of peptides recognized by PDZ domains, on
217                   The functionally tolerated sequence space of proteins can now be explored in an unp
218 s that describes the currently known natural sequence space of proteins, we have reannotated all of t
219 but remains a challenge because of the large sequence space of proteins.
220     We applied this selection to examine the sequence space of residues flanking the Nostoc punctifor
221 r N-degrons in the lysine (K)-asparagine (N) sequence space of the 14-residue peptides containing eit
222 ntly expand the collection of cas genes: the sequence space of the Cas9 family, the key player in the
223 ve sequence analysis was used to explore the sequence space of the RA motif within ribosomal RNAs in
224  a small library that encompasses the entire sequence space of two amino acids should be of use in ma
225 cted to compare experimental and theoretical sequence spaces of tetrameric proto-peptides.
226 strand relative to random coil structure and sequence spacing of Asp, Glu residues.
227  of open reading frames that distils protein sequence space on the basis of three inherent properties
228 er, these results suggest that the volume of sequence space optimal for a protein structure is surpri
229 s with different functions close together in sequence space, pairwise epistasis therefore facilitates
230 S-layer proteins populate a vast and diverse sequence space, performing disparate functions in prokar
231 ein superfamilies, these break new ground in sequence space: promiscuity now connects enzymes with on
232                               The additional sequence space provided by three base pairs allows for t
233  used to drive a Monte Carlo optimization in sequence space: random moves are either accepted or reje
234 ld be characterized by large "leaps" through sequence space rather than isolated point mutations, per
235 or engineering sequence pools that links RNA sequence space regions with corresponding structural dis
236 ays provide only a limited view of the large sequence space relevant to the ribozyme function.
237 ical diversity, success in unlocking protein sequence space remains elusive.
238 y a tiny fraction of the total amount of DNA sequence space represented by this division of life.
239 ry that uniformly samples the manufacturable sequence space, reproducible screening data are generate
240 acity of ribosome display to accommodate the sequence space required for the diverse library builds.
241                        More importantly, the sequence space sampled by RECON MSD resembled the evolut
242 sition of these invalid intermediates in the sequence space, seven of the 30 possible paths consisted
243  underlying distribution of functions across sequence space shaped historical evolution.
244 osomal RNAs in order to define its canonical sequence space signature.
245 nce is strong enough to overcome the size of sequence space so that most native sequences are located
246 space are vastly smaller than the nucleotide sequence space, suggesting a new avenue for finding nove
247       The relative sparsity of paralogues in sequence space suggests that new insulated pathways can
248 uman genome is significantly more compact in sequence space than a random genome.
249 es, which were found to cover a more limited sequence space than HLA-A and -B molecules.
250         Second, ncRNAs command a much larger sequence space than proteins, and can therefore achieve
251  allows ssDNA viruses to access much broader sequence space than through nucleotide substitution and
252 netic system can explore the entire expanded sequence space that additional nucleotides create, a maj
253 s that high mutation rates unlock regions of sequence space that are enriched in positively coupled m
254 n performance were found to map a functional sequence space that correlated well with computational p
255 xperiments that significantly expand the BH3 sequence space that has been experimentally tested for i
256 d-backbone assumption severely restricts the sequence space that is accessible via design.
257                                 The enormous sequence space that is available from 20 amino acids pro
258                   How large is the volume of sequence space that is compatible with a given protein s
259 d distribution of paralogous pathways in the sequence space that is defined by their specificity-dete
260 ctory of functional DHFR through its protein sequence space that lead to the diverged binding and cat
261 rn of connectivity of functional variants in sequence space that likely constrains PhoQ evolution.
262  study also demonstrates unexplored areas of sequence space that may be fruitful for genome mining.
263 stacle in de novo protein design is the vast sequence space that needs to be searched through to obta
264 ic recombination explores a unique subset of sequence space that promotes rapid molecular diversifica
265 ar structure is modeled as a random graph in sequence space (the so-called neutral network).
266 ity of these two activities within a defined sequence space, the complete set of all intermediate seq
267 ablished tool to explore confined regions in sequence space, the generation of functional hybrid prot
268 R Interface" displays predictive analyses in sequence space; the "CrystalPainter" maps evolutionary c
269 by helping organize this unknown metagenomic sequence space, they typically use only approximately 75
270     This represents a necessary expansion of sequence space to accommodate the growing precision and
271 report a methodology that allows the peptide sequence space to be searched for self-assembling struct
272        These tools, which enable the peptide sequence space to be searched for supramolecular propert
273                 Data-driven design navigates sequence space to directly inquire upon how to encode an
274 ng faster and simpler ways to screen protein sequence space to enable the identification of new bioca
275 e virus must traverse a fitness "barrier" in sequence space to escape the host's cytotoxic T-lymphocy
276 esent nomenclature, via a sequential path in sequence space to evaluate the effects of conservative h
277                         We are expanding the sequence space to include over 30 000 human and mouse is
278                      fries pre-processes the sequence space to limit a design to only the most stable
279 high specificity are frequently connected in sequence space to more promiscuous variants that can ser
280 e chaperones promote a deeper exploration of sequence space to strengthen functional PPIs, and dimini
281 ncreasing fidelity, biasing random drifts in sequence space toward 'crystallization.' This region enc
282 e facilitated by following fitness slopes in sequence space underpinned by binding-induced conformati
283                           The exploration of sequence space was accelerated by increasing the mutatio
284                                    Since the sequence space was not completely sampled, higher affini
285 possesses a stable scaffold, a large jump in sequence space was performed by the further addition of
286                           In this simplified sequence space we explore the mutational path from one f
287 rcome the enormity of the potential Bcl-x(L) sequence space, we developed and applied a computational
288 es of RNA Diels-Alderases closely related in sequence space were obtained.
289  provides greater expressivity in regions of sequence space where data are plentiful while still main
290 tive maximum entropy character in regions of sequence space where data are sparse or absent.
291 uide the conformational search of amino acid sequence space, where physicochemical packing is accommo
292 opulations of organisms tightly localized in sequence space, whereas at higher mutation rates, specie
293 qually parsimonious trajectories through RNA sequence space which connect two pairs of sequences that
294 r binding partners to explore regions of the sequence space which correspond to less stable proteins.
295  The tested peptides were mapped in the HVR1 sequence space, which was visualized as a network of 11,
296 ms have evolved mechanisms for exploring DNA sequence space while substantially reducing the hazard t
297 nucleoprotein filament is used to search DNA sequence space within 3D domains of DNA, exploiting mult
298 ary approach was used to expand the testable sequence space within a peptide library of approximately
299              Outer-shell asymmetry increases sequence space without compromising electron transfer fu
300 o maximize the use of available nucleic acid sequence space would have been crucial during the presum

 
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