Beyond Membrane Protein Structure: Drug Discovery, Dynamics and Difficulties

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Beyond Membrane Protein Structure: Drug Discovery, Dynamics and Difficulties is …
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scholarly articleQ13442814

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P356DOI10.1007/978-3-319-35072-1_12
P698PubMed publication ID27553242

P50authorMatteo AldeghiQ58796033
Philip C. BigginQ60636399
P2093author name stringAlexander Heifetz
Michael J Bodkin
P2860cites workEverything you wanted to know about Markov State Models but were afraid to askQ24616866
Computational identification of a transiently open L1/S3 pocket for reactivation of mutant p53Q24628577
Predicting absolute ligand binding free energies to a simple model siteQ24683618
Markov state models provide insights into dynamic modulation of protein functionQ26861597
Exploiting protein intrinsic flexibility in drug designQ38180428
Drug-target residence time--a case for G protein-coupled receptorsQ38189272
Systems biology brings new dimensions for structure-based drug designQ38233920
Investigating drug-target association and dissociation mechanisms using metadynamics-based algorithmsQ38286343
Computational challenges of structure-based approaches applied to HIV.Q38364829
Design strategies to address kinetics of drug binding and residence timeQ38381796
Structure versus function-The impact of computational methods on the discovery of specific GPCR-ligandsQ38398083
AMPA receptor-positive allosteric modulators for the treatment of schizophrenia: an overview of recent patent applicationsQ38421802
Pentameric Ligand-gated Ion Channels : Insights from ComputationQ38452843
Ligand Residence Time at G-protein-Coupled Receptors-Why We Should Take Our Time To Study It.Q38543639
The Dynamics of Drug Discovery.Q38544120
Direct calculation of the binding free energies of FKBP ligandsQ39131231
Agonist and antagonist binding in human glycine receptorsQ39135614
Hydration Site Thermodynamics Explain SARs for Triazolylpurines Analogues Binding to the A2A ReceptorQ39159119
Compounds designed to fit a site of known structure in human haemoglobinQ40016796
A Strategy for the Chemotherapy of Infectious DiseaseQ40081247
On-the-Fly Learning and Sampling of Ligand Binding by High-Throughput Molecular Simulations.Q40308189
Functional insight into development of positive allosteric modulators of AMPA receptors.Q41784821
Toward an understanding of agonist binding to human Orexin-1 and Orexin-2 receptors with G-protein-coupled receptor modeling and site-directed mutagenesisQ41807597
MemProtMD: Automated Insertion of Membrane Protein Structures into Explicit Lipid Membranes.Q42072255
Stereocontrolled synthesis and pharmacological evaluation of azetidine-2,3-dicarboxylic acids at NMDA receptorsQ42164772
Molecular simulations with solvent competition quantify water displaceability and provide accurate interaction maps of protein binding sitesQ42184980
A conserved aromatic lock for the tryptophan rotameric switch in TM-VI of seven-transmembrane receptorsQ42241635
Functional efficacy of adenosine A₂A receptor agonists is positively correlated to their receptor residence timeQ42246408
NMDA receptor modulators: an updated patent review (2013-2014)Q26997407
Structure-based virtual screening for drug discovery: a problem-centric reviewQ27022502
Mechanisms for activation and antagonism of an AMPA-sensitive glutamate receptor: crystal structures of the GluR2 ligand binding coreQ27628494
Predicting Ligand Binding Affinity with Alchemical Free Energy Methods in a Polar Model Binding SiteQ27657572
Biostructural and pharmacological studies of bicyclic analogues of the 3-isoxazolol glutamate receptor agonist ibotenic acidQ27665730
Integration of lead optimization with crystallography for a membrane-bound ion channel target: discovery of a new class of AMPA receptor positive allosteric modulatorsQ27666167
Structure based evolution of a novel series of positive modulators of the AMPA receptorQ27666428
Structural and Functional Analysis of Two New Positive Allosteric Modulators of GluA2 Desensitization and DeactivationQ27667701
Structure-kinetic relationship study of CDK8/CycC specific compoundsQ27677859
Functional analysis of a novel positive allosteric modulator of AMPA receptors derived from a structure-based drug design strategyQ27681406
Pharmacological and structural characterization of conformationally restricted (S)-glutamate analogues at ionotropic glutamate receptorsQ27681743
Chemoenzymatic synthesis of new 2,4-syn-functionalized (S)-glutamate analogues and structure-activity relationship studies at ionotropic glutamate receptors and excitatory amino acid transportersQ27684003
Molecular recognition of two 2,4-syn-functionalized (S)-glutamate analogues by the kainate receptor GluK3 ligand binding domainQ27694588
Binding mode of an α-amino acid-linked quinoxaline-2,3-dione analogue at glutamate receptor subtype GluK1Q27700165
Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease inhibitorsQ27731528
Structure-based design of potent inhibitors of scytalone dehydratase: displacement of a water molecule from the active siteQ27766749
Molecular dynamics simulations of GPCR-cholesterol interaction: An emerging paradigmQ28080537
Approaches to the description and prediction of the binding affinity of small-molecule ligands to macromolecular receptorsQ28219491
Extending the power of quantum chemistry to large systems with the fragment molecular orbital methodQ28303024
Molecular mechanism for the dual alcohol modulation of Cys-loop receptorsQ28484223
The role of flexibility and conformational selection in the binding promiscuity of PDZ domainsQ28484777
Drug design for ever, from hype to hopeQ28732341
Study of Human Orexin-1 and -2 G-Protein-Coupled Receptors with Novel and Published Antagonists by Modeling, Molecular Dynamics Simulations, and Site-Directed MutagenesisQ29031166
Modelling three-dimensional protein structures for applications in drug design.Q30355473
Locating missing water molecules in protein cavities by the three-dimensional reference interaction site model theory of molecular solvation.Q30358933
The Confine-and-Release Method: Obtaining Correct Binding Free Energies in the Presence of Protein Conformational ChangeQ30372513
The influence of cholesterol on membrane protein structure, function, and dynamics studied by molecular dynamics simulations.Q30373374
Protein crystallography for aspiring crystallographers or how to avoid pitfalls and traps in macromolecular structure determinationQ30409760
Perspective: Alchemical free energy calculations for drug discoveryQ30422862
Alchemical free energy methods for drug discovery: progress and challengesQ30427576
Evaluating the role of the alpha-7 nicotinic acetylcholine receptor in the pathophysiology and treatment of schizophreniaQ30428422
Complete reconstruction of an enzyme-inhibitor binding process by molecular dynamics simulations.Q30501558
Pathway and mechanism of drug binding to G-protein-coupled receptors.Q30503489
Funnel metadynamics as accurate binding free-energy methodQ30539051
SIGNAL TRANSDUCTION. Structural basis for nucleotide exchange in heterotrimeric G proteinsQ42390741
Mechanism of voltage gating in potassium channelsQ42644041
One Size Does Not Fit All: The Limits of Structure-Based Models in Drug DiscoveryQ42659257
AceCloud: Molecular Dynamics Simulations in the CloudQ42695719
Quantifying water-mediated protein-ligand interactions in a glutamate receptor: a DFT studyQ42739559
A comparative analysis of the role of water in the binding pockets of ionotropic glutamate receptors.Q42881770
Computational drug design accommodating receptor flexibility: the relaxed complex schemeQ43992973
Water network perturbation in ligand binding: adenosine A(2A) antagonists as a case study.Q44760042
The translocation kinetics of antibiotics through porin OmpC: insights from structure-based solvation mapping using WaterMapQ45855155
Contributions of water transfer energy to protein-ligand association and dissociation barriers: Watermap analysis of a series of p38α MAP kinase inhibitorsQ46377411
Extracting hydration sites around proteins from explicit water simulationsQ46636331
Thermodynamics of buried water clusters at a protein-ligand binding interfaceQ46938920
Comparison of several molecular docking programs: pose prediction and virtual screening accuracy.Q47708648
Rigorous Free Energy Calculations in Structure-Based Drug Design.Q51613137
Novel 6,7,8,9-tetrahydro-5H-1,4,7,10a-tetraaza-cyclohepta[f]indene analogues as potent and selective 5-HT(2C) agonists for the treatment of metabolic disorders.Q53447679
Structure- and property-based design of factor Xa inhibitors: Pyrrolidin-2-ones with acyclic alanyl amides as P4 motifsQ56975993
CopernicusQ57082059
Structure–Affinity Relationships (SARs) and Structure–Kinetics Relationships (SKRs) of Kv11.1 BlockersQ63916704
Analysis of ligand-bound water molecules in high-resolution crystal structures of protein-ligand complexes.Q64977617
Thermodynamic contributions of the ordered water molecule in HIV-1 proteaseQ73442110
Partial agonist activity of 11-cis-retinal in rhodopsin mutantsQ73674599
4-Anilino-6,7-dialkoxyquinoline-3-carbonitrile inhibitors of epidermal growth factor receptor kinase and their bioisosteric relationship to the 4-anilino-6,7-dialkoxyquinazoline inhibitorsQ74247151
The effect of water displacement on binding thermodynamics: concanavalin AQ79934379
Understanding kinase selectivity through energetic analysis of binding site watersQ83030277
Computational sampling of a cryptic drug binding site in a protein receptor: explicit solvent molecular dynamics and inhibitor docking to p38 MAP kinaseQ83158635
Ligand mapping on protein surfaces by the 3D-RISM theory: toward computational fragment-based drug designQ84351224
Molecular dynamics simulations of membrane proteinsQ85831701
Docking challenge: protein sampling and molecular docking performanceQ30607323
Involvement of water in carbohydrate-protein binding.Q30666622
Data sharing mattersQ30735723
The use of thermodynamic and kinetic data in drug discovery: decisive insight or increasing the puzzlement?Q30881748
Virtual screening of chemical librariesQ33209939
A high-throughput de novo sequencing approach for shotgun proteomics using high-resolution tandem mass spectrometry.Q33537380
Mapping of allosteric druggable sites in activation-associated conformers of the M2 muscarinic receptorQ33577530
Computational analysis of the binding specificity of Gleevec to Abl, c-Kit, Lck, and c-Src tyrosine kinasesQ33631185
Not just an oil slick: how the energetics of protein-membrane interactions impacts the function and organization of transmembrane proteins.Q33736493
Do crystal structures obviate the need for theoretical models of GPCRs for structure-based virtual screening?Q34049826
Molecular dynamics simulations and drug discoveryQ34061019
Hierarchical coarse-graining strategy for protein-membrane systems to access mesoscopic scalesQ34127406
Molecular signatures of G-protein-coupled receptorsQ34327700
Structural determinants and mechanism of action of a GluN2C-selective NMDA receptor positive allosteric modulator.Q34360057
GPCRDB: an information system for G protein-coupled receptorsQ34389708
Accurate and reliable prediction of relative ligand binding potency in prospective drug discovery by way of a modern free-energy calculation protocol and force fieldQ34459931
Discovery of a novel binding trench in HIV integrase.Q34546744
Fighting obesity with a sugar-based library: discovery of novel MCH-1R antagonists by a new computational-VAST approach for exploration of GPCR binding sitesQ34670175
Reduced lateral mobility of lipids and proteins in crowded membranesQ34671799
Role of Desolvation in Thermodynamics and Kinetics of Ligand Binding to a KinaseQ34680443
Role of the active-site solvent in the thermodynamics of factor Xa ligand bindingQ34748976
Microsecond simulations indicate that ethanol binds between subunits and could stabilize an open-state model of a glycine receptorQ34772214
On the nature of partial agonism in the nicotinic receptor superfamilyQ34797005
Conformational changes in talin on binding to anionic phospholipid membranes facilitate signaling by integrin transmembrane helicesQ35034161
Absolute binding free energy calculations using molecular dynamics simulations with restraining potentialsQ35051978
AMPA receptor potentiators: from drug design to cognitive enhancementQ35054673
Kinetics of protein-ligand unbinding: Predicting pathways, rates, and rate-limiting stepsQ35062738
Predictive power of molecular dynamics receptor structures in virtual screeningQ35073109
Current progress in Structure-Based Rational Drug Design marks a new mindset in drug discoveryQ35136572
Homology Model Versus X-ray Structure in Receptor-based Drug Design: A Retrospective Analysis with the Dopamine D3 ReceptorQ35181896
Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptaseQ35243844
Structure-based virtual screening for drug discovery: principles, applications and recent advances.Q35282223
Rational Design of a Novel AMPA Receptor Modulator through a Hybridization ApproachQ35379102
Molecular blueprint of allosteric binding sites in a homologue of the agonist-binding domain of the α7 nicotinic acetylcholine receptor.Q35616147
Structural biology. Structural basis for chemokine recognition and activation of a viral G protein-coupled receptorQ35652476
Receptor-based virtual screening protocol for drug discovery.Q35653355
From G Protein-coupled Receptor Structure Resolution to Rational Drug Design.Q35671393
Computationally-guided optimization of a docking hit to yield catechol diethers as potent anti-HIV agentsQ35673318
GPCR structure, function, drug discovery and crystallography: report from Academia-Industry International Conference (UK Royal Society) Chicheley Hall, 1-2 September 2014.Q35830953
Molecular determinants of selectivity and efficacy at the dopamine D3 receptor.Q36153010
Molecular mechanism of 7TM receptor activation--a global toggle switch modelQ36364704
Accurate calculation of the absolute free energy of binding for drug moleculesQ36427764
Explaining why Gleevec is a specific and potent inhibitor of Abl kinaseQ36582978
Calculation of protein-ligand binding affinities.Q36698596
An improved relaxed complex scheme for receptor flexibility in computer-aided drug designQ36838120
Are predicted protein structures of any value for binding site prediction and virtual ligand screening?Q36859642
A combined bioinformatics and chemoinformatics approach for developing asymmetric bivalent AMPA receptor positive allosteric modulators as neuroprotective agentsQ37069448
Subtype selective kainic acid receptor agonists: discovery and approaches to rational designQ37214843
Efficient drug lead discovery and optimizationQ37307959
Binding of small-molecule ligands to proteins: "what you see" is not always "what you get".Q37372747
Energetics of displacing water molecules from protein binding sites: consequences for ligand optimizationQ37439036
The therapeutic promise of positive allosteric modulation of nicotinic receptorsQ37695734
Prediction of protein-ligand binding affinity by free energy simulations: assumptions, pitfalls and expectationsQ37761334
Limiting assumptions in structure-based design: binding entropyQ37972732
New insights from structural biology into the druggability of G protein-coupled receptors.Q37998740
A crystal clear solution for determining G-protein-coupled receptor structuresQ38025530
Comparing proteins by their internal dynamics: exploring structure-function relationships beyond static structural alignmentsQ38064010
AMPA receptor positive allosteric modulators: a patent reviewQ38081162
P407language of work or nameEnglishQ1860
P921main subjectmembrane proteinQ423042
drug discoveryQ1418791
P304page(s)161-181
P577publication date2016-01-01
P1433published inAdvances in Experimental Medicine and BiologyQ4686385
P1476titleBeyond Membrane Protein Structure: Drug Discovery, Dynamics and Difficulties
P478volume922

Reverse relations

Q47348631Computational Methods Used in Hit-to-Lead and Lead Optimization Stages of Structure-Based Drug Discoverycites workP2860

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