Bin W Zhang, Mikolai Fajer, Wei Chen, Francesca Moraca, Lingle Wang
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引用次数: 0
Abstract
As the name implies, structure-based drug design requires confidence in the holo complex structure. The ability to clarify which protein conformation to use when ambiguity arises would be incredibly useful. We present a large scale validation of the computational method Protein Reorganization Free Energy Perturbation (PReorg-FEP) and demonstrate its quantitative accuracy in selecting the correct protein conformation among candidate models in apo or ligand induced states for 14 different systems. These candidate conformations are pulled from various drug discovery related campaigns: cryptic conformations induced by novel hits in lead identification, binding site rearrangement during lead optimization, and conflicting structural biology models. We also show an example of a pH-dependent conformational change, relevant to protein design.
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The Journal of Chemical Information and Modeling publishes papers reporting new methodology and/or important applications in the fields of chemical informatics and molecular modeling. Specific topics include the representation and computer-based searching of chemical databases, molecular modeling, computer-aided molecular design of new materials, catalysts, or ligands, development of new computational methods or efficient algorithms for chemical software, and biopharmaceutical chemistry including analyses of biological activity and other issues related to drug discovery.
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