Lance M. Westerhoff
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View article: Atomic Detail from Disordered Regions: QM/MM-Based Real-Space Reconstruction ofLoops, Rotamers, and Protonation States in X-ray/Cryo-EM Density
Atomic Detail from Disordered Regions: QM/MM-Based Real-Space Reconstruction ofLoops, Rotamers, and Protonation States in X-ray/Cryo-EM Density Open
Protein flexibility is central to function—governing allosteric regulation, catalysis, signal transduction, and drug binding. Yet, this flexibility is often underrepresented in structural models derived from X-ray or Cryo-EM experiments, w…
View article: Recent Advances in Practical Quantum Mechanics and M<scp>ixed‐QM</scp>/<scp>MM</scp>‐Driven X‐Ray Crystallography and Cryogenic Electron Microscopy (<scp>Cryo‐EM</scp>) and Their Impact on Structure‐Based Drug Discovery
Recent Advances in Practical Quantum Mechanics and M<span>ixed‐QM</span>/<span>MM</span>‐Driven X‐Ray Crystallography and Cryogenic Electron Microscopy (<span>Cryo‐EM</span>) and Their Impact on Structure‐Based Drug Discovery Open
With the steady, decades-long advance of faster, smarter computers, structure-based drug discovery (SBDD) and computer-aided drug design (CADD) have become indispensable tools for pharmaceutical research. Today, most pharmaceutical compani…
View article: Free Energy Calculations Using the Movable Type Method with Molecular Dynamics Driven Protein–Ligand Sampling
Free Energy Calculations Using the Movable Type Method with Molecular Dynamics Driven Protein–Ligand Sampling Open
Fast and accurate biomolecular free energy estimation has been a significant interest for decades, and with recent advances in computer hardware, interest in new method development in this field has even grown. Thorough configurational sta…
View article: MovableType Software for Fast Free Energy-Based Virtual Screening: Protocol Development, Deployment, Validation, and Assessment
MovableType Software for Fast Free Energy-Based Virtual Screening: Protocol Development, Deployment, Validation, and Assessment Open
For decades, the complicated energy surfaces found in macromolecular protein:ligand structures, which require large amounts of computational time and resources for energy state sampling, have been an inherent obstacle to fast, routine free…
View article: Locating H atoms: active-site protomer/tautomer state determination using routine macromolecular X-ray diffraction and <i>BUSTER</i>/<i>DivCon</i>
Locating H atoms: active-site protomer/tautomer state determination using routine macromolecular X-ray diffraction and <i>BUSTER</i>/<i>DivCon</i> Open
Active site protonation states play a critical role in enzyme mechanisms of action and understanding these states -in ligands, cofactors, and pocket residues -can be integral to successful structure based drug design (SBDD) campaigns.Neutr…
View article: High-throughput quantum-mechanics/molecular-mechanics (ONIOM) macromolecular crystallographic refinement with<i>PHENIX</i>/<i>DivCon</i>: the impact of mixed Hamiltonian methods on ligand and protein structure
High-throughput quantum-mechanics/molecular-mechanics (ONIOM) macromolecular crystallographic refinement with<i>PHENIX</i>/<i>DivCon</i>: the impact of mixed Hamiltonian methods on ligand and protein structure Open
Conventional macromolecular crystallographic refinement relies on often dubious stereochemical restraints, the preparation of which often requires human validation for unusual species, and on rudimentary energy functionals that are devoid …
View article: Fast, accurate X-ray density-driven ligand docking on the free energy surface using the MovableType method coupled with <i>Phenix</i>/<i>DivCon</i>
Fast, accurate X-ray density-driven ligand docking on the free energy surface using the MovableType method coupled with <i>Phenix</i>/<i>DivCon</i> Open
X-ray crystallography is the primarily technique used to determine the three-dimensional (3D) structure of protein:ligand and protein:protein complexes, and it plays a central role in Structure Based Drug Design (SBDD).Recently, we integra…
View article: Modern rigorous macromolecular crystallographic refinement using mixed QM/MM functional methods as implemented in <i>DivCon</i>
Modern rigorous macromolecular crystallographic refinement using mixed QM/MM functional methods as implemented in <i>DivCon</i> Open
Conventional macromolecular crystallographic refinement relies on stereochemistry restraints and rudimentary energy functionals to ensure the correct geometry of the model of the macromolecule, along with any bound ligand(s), within the ex…
View article: <i>XModeScore</i>: a novel method for accurate protonation/tautomer-state determination using quantum-mechanically driven macromolecular X-ray crystallographic refinement
<i>XModeScore</i>: a novel method for accurate protonation/tautomer-state determination using quantum-mechanically driven macromolecular X-ray crystallographic refinement Open
Gaining an understanding of the protein–ligand complex structure along with the proper protonation and explicit solvent effects can be important in obtaining meaningful results in structure-guided drug discovery and structure-based drug di…