A5005498993- Protein Structure and Dynamics
- Computational Drug Discovery Methods
- Enzyme Structure and Function
- Biochemical and Molecular Research
- RNA and protein synthesis mechanisms
- Pharmacogenetics and Drug Metabolism
- Receptor Mechanisms and Signaling
- Chemical Synthesis and Analysis
- DNA and Nucleic Acid Chemistry
- Monoclonal and Polyclonal Antibodies Research
- Colorectal Cancer Treatments and Studies
- Spectroscopy and Quantum Chemical Studies
- Lipid Membrane Structure and Behavior
- Microbial Metabolic Engineering and Bioproduction
- Mass Spectrometry Techniques and Applications
- Click Chemistry and Applications
- Genomics and Chromatin Dynamics
- Trypanosoma species research and implications
- Drug Transport and Resistance Mechanisms
- Photosynthetic Processes and Mechanisms
- Protein purification and stability
- Chemical Reactions and Isotopes
- Analytical Chemistry and Chromatography
- Glycosylation and Glycoproteins Research
- thermodynamics and calorimetric analyses
Heidelberg Institute for Theoretical Studies
2016-2025
Heidelberg University
2016-2025
DKFZ-ZMBH Alliance
2016-2025
Heidelberg University
2017-2025
Klaus Tschira Foundation
2023
University of Modena and Reggio Emilia
2011-2022
Aboca (Italy)
2022
Excel Life Sciences (India)
2022
Gdańsk Medical University
2022
Sanofi (France)
2021
Abstract Structure-based drug design has often been restricted by the rather static picture of protein–ligand complexes presented crystal structures, despite widely accepted importance protein flexibility in biomolecular recognition. Here we report a detailed experimental and computational study target, human heat shock 90, to explore contribution dynamics binding thermodynamics kinetics drug-like compounds. We observe that their properties depend on whether loop or helical conformation site...
Drug-target residence time (τ), one of the main determinants drug efficacy, remains highly challenging to predict computationally and, therefore, is usually not considered in early stages design. Here, we present an efficient computational method, τ-random acceleration molecular dynamics (τRAMD), for ranking candidates by their and obtaining insights into ligand-target dissociation mechanisms. We assessed τRAMD on a data set 70 diverse drug-like ligands N-terminal domain HSP90α,...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNew hydrogen-bond potentials for use in determining energetically favorable binding sites on molecules of known structureDavid N. A. Boobbyer, Peter J. Goodford, M. McWhinnie, and Rebecca C. WadeCite this: Med. Chem. 1989, 32, 5, 1083–1094Publication Date (Print):May 1, 1989Publication History Published online1 May 2002Published inissue 1 1989https://pubs.acs.org/doi/10.1021/jm00125a025https://doi.org/10.1021/jm00125a025research-articleACS...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPrediction of Drug Binding Affinities by Comparative Energy AnalysisAngel R. Ortiz, M. Teresa Pisabarro, Federico Gago, and Rebecca C. WadeCite this: J. Med. Chem. 1995, 38, 14, 2681–2691Publication Date (Print):July 1, 1995Publication History Published online1 May 2002Published inissue 1 July 1995https://pubs.acs.org/doi/10.1021/jm00014a020https://doi.org/10.1021/jm00014a020research-articleACS PublicationsRequest reuse permissionsArticle...
The pH-dependent characteristics of a protein are determined by the pKas its titratable residues. Continuum electrostatic approaches provide fast means calculating residues in proteins immersed aqueous ionic solution. Here, we show how optimization parameters used continuum calculations can lead to significant improvements accuracy pKa predictions. Dependence on dielectric constant is studied, and two classes ionizable sites identified: (1) large number mostly solvent exposed for which best...
The specificity of interactions between biological macromolecules and their ligands may be partially attributed to the directional properties hydrogen bonds. We have now extended GRID method (Goodford, P. J. Med. Chem. 1985, 28, 849. Boobbyer, D. N. A.; Goodford, J.; McWhinnie, M.; Wade, R. C. 1989, 32, 1083), determining energetically favorable ligand binding sites on molecules known structure, in order improve treatment groups which can make multiple In this method, interaction energy a...
Abstract Given the three‐dimensional structure of a protein, how can one find sites where other molecules might bind to it? Do these have properties necessary for high affinity binding? Is this protein suitable target drug design? Here, we discuss recent developments in computational methods address and related questions. Geometric identify pockets on surfaces been developed over many years but, with new algorithms, their performance is still improving. Simulation show promise accounting...
To bind at an enzyme’s active site, a ligand must diffuse or be transported to the surface, and, if binding site is buried, through protein reach it. Although driving force for often ascribed hydrophobic effect, electrostatic interactions also influence process of both charged and nonpolar ligands. First, steering substrates into enzyme sites discussed. This particular relevance diffusion-influenced enzymes. By comparing results Brownian dynamics simulations potential similarity analysis...
We present the results for CAPRI Round 30, first joint CASP-CAPRI experiment, which brought together experts from protein structure prediction and protein-protein docking communities. The comprised 25 targets amongst those submitted CASP11 experiment of 2014. included mostly homodimers, a few homotetramers, two heterodimers, chains that could readily be modeled using templates Protein Data Bank. On average 24 groups 7 CASP predictions each target, 12 per target participated in scoring...
The microsomal, membrane-bound, human cytochrome P450 (CYP) 2C9 is a liver-specific monooxygenase essential for drug metabolism. CYPs require electron transfer from the membrane-bound CYP reductase (CPR) catalysis. structural details and functional relevance of CYP-membrane interaction are not understood. From multiple coarse grained molecular simulations started with arbitrary configurations protein-membrane complexes, we found two predominant orientations CYP2C9 in membrane, both...