1 we report a series of novel and D3R crystal
structure-guided 4-phenylpiperazines with exceptionally
2 The
structure guided a bioinformatic screen to identify pote
3 Structure-guided addition of a metal-binding pharmacopho
4 riant-specific association information using
structure-guided aggregation of signal.
5 e m102.4-NiV interaction, demonstrating that
structure-guided alanine-scanning and computational mode
6 Herein, we used
structure-guided alanine-scanning mutagenesis to map the
7 Structure-guided alterations of amino acid residues in F
8 Using
structure-guided amino acid substitutions, we increased
9 ne their potency to nanomolar levels through
structure-guided analogue design.
10 By site-directed mutagenesis and
structure-guided analyses, we dissected the function of
11 d to a CoA-alphaSyn conjugate, together with
structure-guided analysis of mutational effects on catal
12 n of a highly selective DAGL inhibitor using
structure-guided and a chemoproteomics strategy to chara
13 Using a
structure-guided and flow chemistry-enabled study of str
14 Using a
structure-guided and fragment-based library approach, we
15 Here, we utilize a sequence
structure guided approach based on a homology model of S
16 re and a refined binding model allowed for a
structure guided approach.
17 ery also underscores the capabilities of the
structure-guided approach in assigning functions of unch
18 e drug leads, which has been a commonly used
structure-guided approach in the past.
19 The proof of concept for a
structure-guided approach targeting the dimerization int
20 l structures of both enzymes, we have used a
structure-guided approach to develop a novel series of i
21 Through a
structure-guided approach, we develop a small-molecule i
22 Using a
structure-guided approach, we exploited a newly discover
23 By using a
structure-guided approach, we uncovered the function of
24 mitations have been mitigated through recent
structure-guided approaches and include trimer-stabilizi
25 he individual residual contributions through
structure-guided approaches may be pivotal for the ratio
26 With a combination of evolutionary and
structure-guided approaches, a set of chimeras were crea
27 DNA-RNA CRISPR and tracr molecules based on
structure-guided approaches.
28 Structural analysis, together with
structure-guided biochemical characterization, uncovered
29 Structure-guided biochemical, mutational, computational,
30 Thus, CPTX represents a prototype for
structure-guided biologics that can efficiently repair o
31 rained Folding algorithm), predicts a nested
structure guided by a maximal subset of positive basepai
32 ing an optimized dielectric-metal-dielectric
structure guided by analytical and quantitative principl
33 omplex landscape of nonequilibrium colloidal
structures, guided by biological design principles.
34 y (AIDA) for assembling multi-domain protein
structures, guided by the ab initio folding potential.
35 A
structure-guided campaign afforded additive improvements
36 The
structure-guided cell-based inhibition studies further d
37 Structure-guided changes in NmeCas9 orthologs convert th
38 Here we describe a
structure-guided chemical approach to covalently and spe
39 Fragment library screening, followed by
structure-guided chemical elaboration of hits, led to th
40 the possible impact on future ligand and/or
structure-guided chemical optimizations, as well as oppo
41 A
structure-guided comparison of these linker proteins ide
42 ctor in the 2-position that was optimized by
structure-guided compound design.
43 ent-based and high-throughput screening with
structure-guided compound elaboration has yielded a tool
44 Here we present mCSM-lig, a
structure-guided computational approach for quantifying
45 Herein, we have used
structure-guided computational screening and optimizatio
46 Here, we utilized
structure-guided cysteine cross-linking and proteolysis-
47 This study provides a
structure-guided definition of the PIRs and a molecular
48 Furthermore,
structure-guided derivatives with an altered piperidine
49 Structure guided design and reverse genetics were used t
50 Here, using
structure guided design of the murine STING CDN binding
51 Here, we used X-ray
structure guided design to optimize our previously descr
52 Using
structure guided design, we optimized a fragment that bo
53 imately 0.2-800 microM were engineered using
structure-guided design and a high-throughput screening
54 Using
structure-guided design and directed protein evolution,
55 We report the
structure-guided design and group-based optimization of
56 late stage optimization efforts including a
structure-guided design and water displacement strategy
57 h, we combined evolutionary information with
structure-guided design and yeast surface display to pro
58 A
structure-guided design approach using a homology model
59 A
structure-guided design approach was employed to exploit
60 This proof-of-principle that
structure-guided design can lead to drug-like molecules
61 Here, we describe the
structure-guided design of a new fluorescent probe (BOFP
62 tain key compounds and set the stage for the
structure-guided design of better translation inhibitors
63 n interface, thus paving the way to a future
structure-guided design of cell adhesion inhibitors agai
64 therapeutic intervention in cancer: from the
structure-guided design of chemical chaperones to restor
65 The
structure-guided design of chloride-conducting channelrh
66 Here, we report the
structure-guided design of hbeta4GalT7 inhibitors.
67 Herein, we report the crystal-
structure-guided design of highly stable RNA nanotriangl
68 We report the
structure-guided design of HIV-1 cyclically permuted gp1
69 Affinity maturation and
structure-guided design of multivalency yielded a trival
70 Here, we report the
structure-guided design of peptide Hr10 and a modified f
71 strate binding and catalysis and may aid the
structure-guided design of specific LCP inhibitors.
72 eds of liganded structures in support of our
structure-guided design process, demonstrating the feasi
73 Env-
structure-guided design strategies resulted in multiple
74 Here we show a
structure-guided design strategy that, by truncation and
75 A
structure-guided design strategy was used to improve the
76 Here, we employed a
structure-guided design to convert a known Hsp90 inhibit
77 We here employ computational and
structure-guided design to develop improved native-like
78 irtual screening, x-ray crystallography, and
structure-guided design to develop opabactin (OP), an ab
79 We used computational and
structure-guided design to develop two next-generation N
80 equencing, computational bioinformatics, and
structure-guided design to enhance the neutralization po
81 of protein-protein interactions and enables
structure-guided design to improve antiviral potency and
82 Structure-guided design was used to generate a series of
83 More recently, use of
structure-guided design with fragment-based drug discove
84 Here we report the
structure-guided design, chemical synthesis and biologic
85 X-ray crystallography enabled
structure-guided design, leading to the identification o
86 Using
structure-guided design, several cell based assays, and
87 throughput screening campaign and subsequent
structure-guided design, we identify small-molecule inhi
88 Using
structure-guided design, we made a series of mutations a
89 ) hit and progressed via iterative cycles of
structure-guided design.
90 Here, we present the
structure guided development of a series of N,N-dimethyl
91 we describe in detail the identification and
structure guided development of Ras-PDEdelta inhibitors
92 Here, we describe a
structure-guided development of a series of covalent and
93 s study represents an example of successful,
structure-guided development of low molecular weight inh
94 This paper describes the
structure-guided development of small molecule inhibitor
95 Here, we describe the
structure-guided development of XL177A, which irreversib
96 ure and function of GPCRs should enhance the
structure-guided discovery of novel chemical tools with
97 d Paraburkholderia phytofirmans coupled with
structure-guided disulfide cross-linking in P. aeruginos
98 site between FluA and FluB PB2 and will aid
structure-guided drug design efforts to identify dual in
99 nhibitors of the XPA-DNA interaction through
structure-guided drug design efforts.
100 Structure-guided drug design relies on detailed structur
101 The use of
structure-guided drug design techniques provided compoun
102 binding and antigenicity and support further
structure-guided drug design.
103 selective covalent FGFR4 inhibitor, through
structure-guided drug design.
104 s of protein complexes is the cornerstone of
structure-guided drug design.
105 y relevant inactive conformation may advance
structure-guided drug development.
106 The use of protein crystallography in
structure-guided drug discovery emerged as enzyme struct
107 findings lay out an important framework for
structure-guided drug discovery targeting MCTs.
108 d-binding site is an important first step in
structure-guided drug discovery, but current methods do
109 Ca(v) ligands and establish a framework for
structure-guided drug discovery.
110 hly disordered structure challenges rational
structure-guided drug discovery.
111 083, and establishes a foundation for future
structure-guided efforts to develop the next generation
112 gments bound to the active site, followed by
structure-guided elaboration to design potent nanomolar
113 Here we describe
structure-guided engineering of a CRISPR-Cas9 complex to
114 the channelrhodopsin pore model via crystal
structure-guided engineering of next-generation light-ac
115 Here we describe
structure-guided engineering of SECURE-ABE variants with
116 against Sudan virus, which enabled rational,
structure-guided engineering to enhance binding and neut
117 Structure-guided engineering was used to refine the bind
118 To test this hypothesis, we developed a
structure-guided evolution approach that does not requir
119 We report the expedient,
structure-guided evolution of weak physiological alloste
120 structures can now serve as templates for a
structure-guided exploration of both conserved and virus
121 Structure-guided exploration of commercial chemical spac
122 we introduce a new computational method for
structure-guided exploration of SAR transfer.
123 Here, we describe the application of a
structure-guided fragment-based drug discovery approach
124 Subsequently,
structure-guided fragment-to-lead optimization led to th
125 Structure-guided functional assays in Drosophila S2 cell
126 This study establishes the utility of
structure-guided functional predictions to enable the di
127 e a molecular blueprint that has facilitated
structure-guided functional remodeling.
128 t 3.14 angstrom resolution, here we report a
structure-guided functional study of 30S substrate recog
129 We suggest incorporation of
structure-guided genetic inference assays into pharmaceu
130 hannelrhodopsin (ChRmine, discovered through
structure-guided genome mining) alongside multiplexed mu
131 Structure-guided growth enabled rapid optimization of po
132 of the E. coli GUS operon is identified, and
structure-guided GusR mutants pinpoint the residues esse
133 A
structure-guided hybridization approach using two privil
134 Structure-guided improvements yield superior affinity re
135 ng domain (LBD) has for many years precluded
structure-guided improvements.
136 The interface defined in this
structure guided in silico modeling, mutagenesis, and in
137 as optimized using a strategy focused on the
structure-guided increase in potency without added lipop
138 nction and represent key steps for advancing
structure-guided inhibitor design to target therapeutica
139 By using CaMKII
structure-guided inhibitor design, we generated four fam
140 nce could be overcome through the use of the
structure-guided inhibitor design.
141 timized against PFKFB3 kinase using critical
structure-guided insights.
142 As a prerequisite for
structure-guided investigation of enzymatic activity, we
143 Here we describe a systematic
structure-guided lead optimization approach of these tan
144 eening assays, fragment-based screening, and
structure-guided ligand design approaches.
145 on functional domains, we propose a protein
structure guided local test (POINT) to provide variant-s
146 Structure-guided manipulation of residues involved in th
147 Structure-guided mapping combined with site-directed mut
148 main III of the E protein, and engineered by
structure-guided methods an antibody directed to it.
149 We have used
structure-guided methods to develop a lead molecule that
150 hese data, together with inhibitor-based and
structure-guided methods, to engineer selective FXIIa in
151 A
structure-guided model of the MepR-mepA operator complex
152 Here, we present a
structure-guided modelling-based strategy for the ration
153 n and synthesis of [Lys(52)]CTX-I(41-60) via
structure-guided modification, a truncated, equipotent a
154 d to unmodified gp120, presumably due to the
structure-guided modifications of the modified gp120 cor
155 746-750) were introduced through a series of
structure-guided modifications.
156 e use of comparative structural analysis and
structure-guided molecular design to develop potent and
157 Structure-guided molecular genetic analyses revealed tha
158 Structure guided mutagenesis studies demonstrated that t
159 Structure guided mutagenesis, cross-linking immunoprecip
160 Overall, this study demonstrates that
structure-guided mutagenesis aids the identification of
161 Structure-guided mutagenesis and docking studies demonst
162 Structure-guided mutagenesis and electrophysiological da
163 Here, we used X-ray
structure-guided mutagenesis and functional studies to i
164 Combined with
structure-guided mutagenesis and in vitro and in vivo cr
165 Pseudomonas fluorescens strain and performed
structure-guided mutagenesis and library screening to ob
166 Structure-guided mutagenesis and mathematical modeling f
167 Structure-guided mutagenesis and molecular dynamics simu
168 Using
structure-guided mutagenesis and neuron-based screening,
169 idated experimentally using a combination of
structure-guided mutagenesis and RNA structure probing.
170 ivated TEV protease that we designed through
structure-guided mutagenesis and screening.
171 ty from the protease activity, we employed a
structure-guided mutagenesis approach and identified res
172 Structure-guided mutagenesis combined with biophysical a
173 Structure-guided mutagenesis confirmed the observed inte
174 bunit stabilizes a high FRET value, which by
structure-guided mutagenesis corresponds to a closed con
175 Structure-guided mutagenesis enabled uncoupling of virul
176 Structure-guided mutagenesis experiments of TarM identif
177 NMR spectroscopy and
structure-guided mutagenesis identified a small hydropho
178 Structure-guided mutagenesis identified residues that co
179 Functional experiments employing
structure-guided mutagenesis in macrophages highlight am
180 Structure-guided mutagenesis indicates that METTL3 is th
181 Extensive
structure-guided mutagenesis of C7 identified three loop
182 Furthermore, we performed
structure-guided mutagenesis of GalA reductases to chang
183 new red-excitable monomeric FPs obtained by
structure-guided mutagenesis of mNeptune.
184 rint, backed-up by automated ligand docking,
structure-guided mutagenesis of OC43, BCoV, and PHEV S1(
185 he greatest activity against acetyl-CoA, and
structure-guided mutagenesis of putative active site res
186 the X-ray crystal structure of SalBIII, and
structure-guided mutagenesis of putative active-site res
187 Structure-guided mutagenesis of residues within the GDP-
188 Our crystal structures, combined with
structure-guided mutagenesis of RGMs and BMP ligands, bi
189 Furthermore,
structure-guided mutagenesis of the binding interface re
190 Structure-guided mutagenesis of the close paralogue SWEE
191 Structure-guided mutagenesis of the complete surface of
192 Structure-guided mutagenesis of the pore residues shows
193 Structure-guided mutagenesis of the proposed substrate-b
194 Structure-guided mutagenesis results show that this cano
195 Structure-guided mutagenesis revealed four catalytic res
196 Structure-guided mutagenesis revealed key contacts of bo
197 Structure-guided mutagenesis reveals that His175, Arg186
198 To address this limitation, we performed a
structure-guided mutagenesis screen to increase the targ
199 d of the nucleobase pocket and we show using
structure-guided mutagenesis that the conserved salt-bri
200 We used
structure-guided mutagenesis to demonstrate that substra
201 Here we used
structure-guided mutagenesis to probe the Rubisco-intera
202 Here, we used x-ray crystallography and
structure-guided mutagenesis to show that an alpha-helic
203 Structure-guided mutagenesis was used to generate antibo
204 Using cryo-electron microscopy,
structure-guided mutagenesis, and cell-based assays, we
205 Using a functional reconstituted DISC,
structure-guided mutagenesis, and quantitative LC-MS/MS,
206 Structure-guided mutagenesis, cell-based zinc uptake ass
207 alysis of JAK2 activation requirements using
structure-guided mutagenesis, cell-signaling assays, mic
208 Structural analysis, combined with
structure-guided mutagenesis, leads us to propose a cata
209 ant mutant SbPAL1 enzymes were generated via
structure-guided mutagenesis, one of which, H123F-SbPAL1
210 Combined with
structure-guided mutagenesis, our studies provide major
211 3811 bound to cAMP, and we confirmed through
structure-guided mutagenesis, the residues important for
212 encing (VIGS), and X-ray crystallography for
structure-guided mutagenesis, to investigate the functio
213 Through
structure-guided mutagenesis, we assessed the role of ke
214 BV and BV adducts of JSC1_58120g3 along with
structure-guided mutagenesis, we have defined residues c
215 By employing
structure-guided mutagenesis, we have identified a mutan
216 Using
structure-guided mutagenesis, we identified key specific
217 Using
structure-guided mutagenesis, we identified upstream ami
218 By performing
structure-guided mutagenesis, we mutated all 38 surface-
219 hetero-PYD/PYD associations, as confirmed by
structure-guided mutagenesis.
220 re, biochemical and physiological studies of
structure-guided mutants are used to show that the hexam
221 Functional evaluation of KAT1
structure-guided mutants at the sensor-pore interfaces s
222 The characterization of
structure-guided mutants illuminates the properties of t
223 p100/IkappaBdelta and functional analysis of
structure-guided mutants, we show that p100/IkappaBdelta
224 Structure-guided mutation allows the generation of a low
225 A
structure-guided mutation in Sestrin2 that decreases its
226 Finally, expression of tubulin with a
structure-guided mutation in the rigosertib-binding pock
227 Structure-guided mutation of a critical residue, F270, t
228 reviously observed for Ly49C.H-2K(b) Indeed,
structure-guided mutation of Ly49C indicated that Ly49C.
229 Structure-guided mutation of the Mmi1(Trp112) residue, w
230 Structure-guided mutational analyses identified residues
231 Structure-guided mutational analyses of RopB dimer inter
232 Evidence from
structure-guided mutational analyses suggests that acyl-
233 Finally,
structure-guided mutational analysis confirms the import
234 Structure-guided mutational analysis converted KATms fro
235 We also performed
structure-guided mutational analysis to survey the funct
236 Using a
structure-guided mutational approach, we showed that mod
237 bind the kinesin motor domain, and selected
structure-guided mutations disrupt KBP inhibition of kin
238 Structure-guided mutations in MYC that disrupt interacti
239 Structure-guided mutations in vitro and in vivo in yeast
240 tory activity, we have investigated a set of
structure-guided mutations of conserved tertiary archite
241 Structure-guided mutations of NreA reduced its nitrate b
242 Structure-guided mutations revealed that the molecular i
243 mechanism for immune system suppression, and
structure-guided mutations show that the Acr proteins bi
244 Structure-guided mutations show that the interface betwe
245 Using
structure-guided mutations, we are able to transfer E. c
246 ent derived lead compound, we have conducted
structure guided optimization that has led to a signific
247 MT revealed key factors important for future
structure-guided optimization delivering IMP-105 (43), a
248 We report the
structure-guided optimization of 3,5-dimethylisoxazole d
249 The HTS-based discovery and
structure-guided optimization of a novel series of GKRP-
250 Herein, we describe the
structure-guided optimization of a series of quinazolino
251 Here we report
structure-guided optimization of an amphipathic peptide,
252 We report the
structure-guided optimization of pyridazine amide spleen
253 nents of the human RNAi pathway have enabled
structure-guided optimization of siRNA properties.
254 The
structure-guided optimization of the pyridone hit 3 usin
255 We now report the
structure-guided optimization of this chemical series ba
256 HTLV-1 PR and provides the basis for further
structure-guided optimization strategies.
257 lo[2,3-b]pyridine LRRK2 inhibitors underwent
structure-guided optimization using this crystallographi
258 A
structure-guided optimization with respect to decreased
259 Thus, virtual screening and
structure-guided optimization yielded newly discovered a
260 Carefully designed
structure-guided or strategically selected disease-assoc
261 Using
structure-guided pharmacophore design followed by dockin
262 evolutionary rate variation and heterodimer
structure-guided phenotyping of AtEDS1 variants and AtPA
263 Structure-guided phylogeny of MCP suggests that Yaraviru
264 A
structure-guided point mutant (R118E) in F1, which block
265 Structure-guided point mutants and the monobody abrogate
266 ormations were selectively disrupted through
structure-guided point mutations to shift single-molecul
267 The ability of in silico tools, including
structure-guided prediction programmes to characterize n
268 Our findings confirm the advantages of
structure-guided protein engineering to design improved
269 These findings enable
structure-guided protein engineering to develop modified
270 Here we used
structure-guided protein engineering to enable microbial
271 Here, we use
structure-guided protein engineering to improve the spec
272 cture analysis, pore vestibule modeling, and
structure-guided protein engineering, we designed and ch
273 Through
structure-guided protein engineering, we generated sever
274 Using
structure-guided protein engineering, we systematically
275 By
structure-guided rational design, ARN3 was converted int
276 ism of endotoxin modification and will aid a
structure-guided rational drug design approach to treati
277 carefully-chosen training sequences made by
structure-guided SCHEMA recombination has enabled us to
278 We have used
structure-guided SCHEMA recombination to create a large
279 Structure-guided separation-of-function mutations show t
280 ain of a PIR from Plasmodium chabaudi We use
structure-guided sequence analysis and molecular modelin
281 Using
structure-guided sequence analysis we uncover previously
282 Furthermore,
structure-guided site-directed mutagenesis indicated tha
283 in silico evolutionary lineage analysis and
structure-guided site-directed mutagenesis with large-sc
284 on in the function of cardiac RyR (RyR2) via
structure-guided site-directed mutagenesis.
285 Structure-guided site-directed mutations converted SLAC1
286 We characterized 100
structure-guided spike designs and identified 26 individ
287 In vivo analysis of
structure-guided STIL mutants reveals distinct binding m
288 Structure-guided studies of key base, sugar, and phospha
289 Structure-guided studies reveal that oncogenic BRAF muta
290 Furthermore, our
structure-guided studies suggest that MoaC catalysis inv
291 have manipulated nucleotide binding through
structure-guided substitutions of an ultraconserved glyc
292 Furthermore,
structure-guided substitutions of residues in the KDM2A
293 We exemplify current developments in
structure-guided target identification and fragment-base
294 This high-resolution
structure guided targeted mutagenesis at the gB-93k inte
295 In this study, we used
structure-guided truncations of the PB2 subunit to show
296 Here, by
structure-guided truncations, confocal microscopy, and c
297 ce of disease-relevant mutations, and that a
structure-guided U2AF(65) variant is capable of manipula
298 Our results provide a roadmap for
structure-guided vaccine development to maximize antibod
299 NA and ARF-Aux/IAA interactions, we analyzed
structure-guided variants of synthetic auxin response ci
300 Structure-guided Zf-GRF mutations impact APE2 DNA bindin