Multiscale methods in drug design bridge chemical and biological complexity in the search for cures

Drug target residence time: a misleading concept

(2018) Rutger H.A. Folmer   DRUG DISCOVERY TODAY

L718Q mutant EGFR escapes covalent inhibition by stabilizing a non-reactive conformation of the lung cancer drug osimertinib

(2018) D. Callegari et al.   Chemical Science

Multiscale analysis of enantioselectivity in enzyme-catalysed ‘lethal synthesis’ using projector-based embedding

(2018) Xinglong Zhang et al.   Royal Society Open Science

PyCGTOOL: Automated Generation of Coarse-Grained Molecular Dynamics Models from Atomistic Trajectories

(2017) James A. Graham et al.   Journal of Chemical Information and Modeling

Metadynamics Simulations Distinguish Short- and Long-Residence-Time Inhibitors of Cyclin-Dependent Kinase 8

(2017) Donatella Callegari et al.   Journal of Chemical Information and Modeling

A Data-Driven Perspective on the Hierarchical Assembly of Molecular Structures

(2017) Lorenzo Boninsegna et al.   Journal of Chemical Theory and Computation

Systematic Quantum Mechanical Region Determination in QM/MM Simulation

(2017) Maria Karelina et al.   Journal of Chemical Theory and Computation

D3R Grand Challenge 2: blind prediction of protein–ligand poses, affinity rankings, and relative binding free energies

(2017) Zied Gaieb et al.   JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN

SEEKR: Simulation Enabled Estimation of Kinetic Rates, A Computational Tool to Estimate Molecular Kinetics and Its Application to Trypsin–Benzamidine Binding

(2017) Lane W. Votapka et al.   JOURNAL OF PHYSICAL CHEMISTRY B

Challenges of Integrating Stochastic Dynamics and Cryo-Electron Tomograms in Whole-Cell Simulations

(2017) Tyler M. Earnest et al.   JOURNAL OF PHYSICAL CHEMISTRY B

Complete protein–protein association kinetics in atomic detail revealed by molecular dynamics simulations and Markov modelling

(2017) Nuria Plattner et al.   Nature Chemistry

ChromEMT: Visualizing 3D chromatin structure and compaction in interphase and mitotic cells

(2017) Horng D. Ou et al.   SCIENCE

ANI-1: an extensible neural network potential with DFT accuracy at force field computational cost

(2017) J. S. Smith et al.   Chemical Science

Physical properties of the HIV-1 capsid from all-atom molecular dynamics simulations

(2017) Juan R. Perilla et al.   Nature Communications

Building bridges between cellular and molecular structural biology

(2017) Ardan Patwardhan et al.   eLife

Low Data Drug Discovery with One-Shot Learning

(2017) Han Altae-Tran et al.   ACS Central Science

Inhibition of prenylated KRAS in a lipid environment

(2017) Johanna M. Jansen et al.   PLoS One

Living on the edge: Simulations of bacterial outer-membrane proteins

(2016) Anna Pavlova et al.   BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

Ligand-Binding Affinity Estimates Supported by Quantum-Mechanical Methods

(2016) Ulf Ryde et al.   CHEMICAL REVIEWS

Coarse-Grained Protein Models and Their Applications

(2016) Sebastian Kmiecik et al.   CHEMICAL REVIEWS

Multi-class and multi-scale models of complex biological phenomena

(2016) Jessica S Yu et al.   CURRENT OPINION IN BIOTECHNOLOGY

Multiscale simulation of DNA

(2016) Pablo D Dans et al.   CURRENT OPINION IN STRUCTURAL BIOLOGY

Predicting Regioselectivity and Lability of Cytochrome P450 Metabolism Using Quantum Mechanical Simulations

(2016) Jonathan D. Tyzack et al.   Journal of Chemical Information and Modeling

Simulation-Based Approaches for Determining Membrane Permeability of Small Compounds

(2016) Christopher T. Lee et al.   Journal of Chemical Information and Modeling

Perspective: Quantum mechanical methods in biochemistry and biophysics

(2016) Qiang Cui   JOURNAL OF CHEMICAL PHYSICS

Perspective: On the importance of hydrodynamic interactions in the subcellular dynamics of macromolecules

(2016) Jeffrey Skolnick   JOURNAL OF CHEMICAL PHYSICS

A Projector-Embedding Approach for Multiscale Coupled-Cluster Calculations Applied to Citrate Synthase

(2016) Simon J. Bennie et al.   Journal of Chemical Theory and Computation

Machine Learning Based Dimensionality Reduction Facilitates Ligand Diffusion Paths Assessment: A Case of Cytochrome P450cam

(2016) J. Rydzewski et al.   Journal of Chemical Theory and Computation

D3R grand challenge 2015: Evaluation of protein–ligand pose and affinity predictions

(2016) Symon Gathiaka et al.   JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN

Controlling the Dissociation of Ligands from the Adenosine A2A Receptor through Modulation of Salt Bridge Strength

(2016) Elena Segala et al.   JOURNAL OF MEDICINAL CHEMISTRY

Role of Molecular Dynamics and Related Methods in Drug Discovery

(2016) Marco De Vivo et al.   JOURNAL OF MEDICINAL CHEMISTRY

Two Relations to Estimate Membrane Permeability Using Milestoning

(2016) Lane W. Votapka et al.   JOURNAL OF PHYSICAL CHEMISTRY B

Structure–Kinetic Relationships of Passive Membrane Permeation from Multiscale Modeling

(2016) Callum J. Dickson et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Design of a hyperstable 60-subunit protein icosahedron

(2016) Yang Hsia et al.   NATURE

A comprehensive map of molecular drug targets

(2016) Rita Santos et al.   NATURE REVIEWS DRUG DISCOVERY

Full-length p53 tetramer bound to DNA and its quaternary dynamics

(2016) Ö Demir et al.   ONCOGENE

Multiscale simulation of molecular processes in cellular environments

(2016) Mara Chiricotto et al.   PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES

Enzyme catalysis by entropy without Circe effect

(2016) Masoud Kazemi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Long antibody HCDR3s from HIV-naïve donors presented on a PG9 neutralizing antibody background mediate HIV neutralization

(2016) Jordan R. Willis et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Transition path theory analysis of c-Src kinase activation

(2016) Yilin Meng et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Visualizing the molecular sociology at the HeLa cell nuclear periphery

(2016) J. Mahamid et al.   SCIENCE

Accurate design of megadalton-scale two-component icosahedral protein complexes

(2016) J. B. Bale et al.   SCIENCE

A Multi-scale Computational Platform to Mechanistically Assess the Effect of Genetic Variation on Drug Responses in Human Erythrocyte Metabolism

(2016) Nathan Mih et al.   PLoS Computational Biology

ReaDDyMM: Fast Interacting Particle Reaction-Diffusion Simulations Using Graphical Processing Units

(2015) Johann Biedermann et al.   BIOPHYSICAL JOURNAL

Molecular Simulations of Gram-Negative Bacterial Membranes: A Vignette of Some Recent Successes

(2015) Jamie Parkin et al.   BIOPHYSICAL JOURNAL

Membrane protein structural biology using X-ray free electron lasers

(2015) Richard Neutze et al.   CURRENT OPINION IN STRUCTURAL BIOLOGY

Using synchrotrons and XFELs for time-resolved X-ray crystallography and solution scattering experiments on biomolecules

(2015) Matteo Levantino et al.   CURRENT OPINION IN STRUCTURAL BIOLOGY

Computation of Hydration Free Energies Using the Multiple Environment Single System Quantum Mechanical/Molecular Mechanical Method

(2015) Gerhard König et al.   Journal of Chemical Theory and Computation

Hybrid Quantum Mechanics/Molecular Mechanics/Coarse Grained Modeling: A Triple-Resolution Approach for Biomolecular Systems

(2015) Pandian Sokkar et al.   Journal of Chemical Theory and Computation

The adaptive buffered force QM/MM method in the CP2K and AMBER software packages

(2015) Letif Mones et al.   JOURNAL OF COMPUTATIONAL CHEMISTRY

Accurate and Reliable Prediction of Relative Ligand Binding Potency in Prospective Drug Discovery by Way of a Modern Free-Energy Calculation Protocol and Force Field

(2015) Lingle Wang et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Kinetics of protein–ligand unbinding: Predicting pathways, rates, and rate-limiting steps

(2015) Pratyush Tiwary et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Membranes serve as allosteric activators of phospholipase A2, enabling it to extract, bind, and hydrolyze phospholipid substrates

(2015) Varnavas D. Mouchlis et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Protein conformational plasticity and complex ligand-binding kinetics explored by atomistic simulations and Markov models

(2015) Nuria Plattner et al.   Nature Communications

Allostery through the computational microscope: cAMP activation of a canonical signalling domain

(2015) Robert D. Malmstrom et al.   Nature Communications

Kinetics of protein-ligand unbinding via smoothed potential molecular dynamics simulations

(2015) Luca Mollica et al.   Scientific Reports

Interaction of the Antimicrobial Peptide Polymyxin B1 with Both Membranes of E. coli: A Molecular Dynamics Study

(2015) Nils A. Berglund et al.   PLoS Computational Biology

Multiscale Estimation of Binding Kinetics Using Brownian Dynamics, Molecular Dynamics and Milestoning

(2015) Lane W. Votapka et al.   PLoS Computational Biology

In pursuit of an accurate spatial and temporal model of biomolecules at the atomistic level: a perspective on computer simulation

(2015) Alan Gray et al.   ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY

Bridging scales through multiscale modeling: a case study on protein kinase A

(2015) Britton W. Boras et al.   Frontiers in Physiology

Investigating Drug–Target Association and Dissociation Mechanisms Using Metadynamics-Based Algorithms

(2014) Andrea Cavalli et al.   ACCOUNTS OF CHEMICAL RESEARCH

QM/MM simulations as an assay for carbapenemase activity in class A β-lactamases

(2014) Ewa I. Chudyk et al.   CHEMICAL COMMUNICATIONS

Finding the right fit: chiseling structures out of cryo-electron microscopy maps

(2014) Elizabeth Villa et al.   CURRENT OPINION IN STRUCTURAL BIOLOGY

Computational modeling of subcellular transport and signaling

(2014) Johan Hake et al.   CURRENT OPINION IN STRUCTURAL BIOLOGY

Cellular and molecular structure as a unifying framework for whole-cell modeling

(2014) Elijah Roberts   CURRENT OPINION IN STRUCTURAL BIOLOGY

Accurate and systematically improvable density functional theory embedding for correlated wavefunctions

(2014) Jason D. Goodpaster et al.   JOURNAL OF CHEMICAL PHYSICS

Extensive all-atom Monte Carlo sampling and QM/MM corrections in the SAMPL4 hydration free energy challenge

(2014) Samuel Genheden et al.   JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN

Predicting hydration free energies with a hybrid QM/MM approach: an evaluation of implicit and explicit solvation models in SAMPL4

(2014) Gerhard König et al.   JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN

Combined Quantum Mechanics/Molecular Mechanics (QM/MM) Simulations for Protein–Ligand Complexes: Free Energies of Binding of Water Molecules in Influenza Neuraminidase

(2014) Christopher J. Woods et al.   JOURNAL OF PHYSICAL CHEMISTRY B

cellPACK: a virtual mesoscope to model and visualize structural systems biology

(2014) Graham T Johnson et al.   NATURE METHODS

Neutron cryo-crystallography captures the protonation state of ferryl heme in a peroxidase

(2014) C. M. Casadei et al.   SCIENCE

Diffuse X-Ray Scattering to Model Protein Motions

(2014) Michael E. Wall et al.   STRUCTURE

A catalytic role for methionine revealed by a combination of computation and experiments on phosphite dehydrogenase

(2014) Kara E. Ranaghan et al.   Chemical Science

A Multiscale Approach to Modelling Drug Metabolism by Membrane-Bound Cytochrome P450 Enzymes

(2014) Richard Lonsdale et al.   PLoS Computational Biology

LipidWrapper: An Algorithm for Generating Large-Scale Membrane Models of Arbitrary Geometry

(2014) Jacob D. Durrant et al.   PLoS Computational Biology

Millisecond-Long Molecular Dynamics Simulations of Proteins on a Special-Purpose Machine

(2013) David E. Shaw   BIOPHYSICAL JOURNAL

Opening windows into the cell: focused-ion-beam milling for cryo-electron tomography

(2013) Elizabeth Villa et al.   CURRENT OPINION IN STRUCTURAL BIOLOGY

Accurate basis set truncation for wavefunction embedding

(2013) Taylor A. Barnes et al.   JOURNAL OF CHEMICAL PHYSICS

Generalized QM/MM Force Matching Approach Applied to the 11-cis Protonated Schiff Base Chromophore of Rhodopsin

(2013) Manuel Doemer et al.   Journal of Chemical Theory and Computation

The Theory of Ultra-Coarse-Graining. 1. General Principles

(2013) James F. Dama et al.   Journal of Chemical Theory and Computation

A stochastic finite element model for the dynamics of globular macromolecules

(2013) Robin C. Oliver et al.   JOURNAL OF COMPUTATIONAL PHYSICS

Quantum Mechanics/Molecular Mechanics Modeling of Regioselectivity of Drug Metabolism in Cytochrome P450 2C9

(2013) Richard Lonsdale et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics

(2013) Gongpu Zhao et al.   NATURE

Cloud-based simulations on Google Exacycle reveal ligand modulation of GPCR activation pathways

(2013) Kai J. Kohlhoff et al.   Nature Chemistry

Photodynamic therapy for photochemists

(2013) S. G. Bown   PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES

Efficient Numerical Reconstruction of Protein Folding Kinetics with Partial Path Sampling and Pathlike Variables

(2013) J. Juraszek et al.   PHYSICAL REVIEW LETTERS

Andrographolide derivatives inhibit guanine nucleotide exchange and abrogate oncogenic Ras function

(2013) H. J. Hocker et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Inteins: nature's gift to protein chemists

(2013) Neel H. Shah et al.   Chemical Science

Computational identification of a transiently open L1/S3 pocket for reactivation of mutant p53

(2013) Christopher D. Wassman et al.   Nature Communications

A Coarse-Grained Protein Model in a Water-like Solvent

(2013) Sumit Sharma et al.   Scientific Reports

Computational Assay of H7N9 Influenza Neuraminidase Reveals R292K Mutation Reduces Drug Binding Affinity

(2013) Christopher J. Woods et al.   Scientific Reports

Back to the Future: Can Physical Models of Passive Membrane Permeability Help Reduce Drug Candidate Attrition and Move Us Beyond QSPR?

(2012) Robert V. Swift et al.   Chemical Biology & Drug Design

Lattice microbes: High-performance stochastic simulation method for the reaction-diffusion master equation

(2012) Elijah Roberts et al.   JOURNAL OF COMPUTATIONAL CHEMISTRY

Unassisted Transport of N-Acetyl-l-tryptophanamide through Membrane: Experiment and Simulation of Kinetics

(2012) Alfredo E. Cardenas et al.   JOURNAL OF PHYSICAL CHEMISTRY B

Ab Initio Quantum Chemistry for Protein Structures

(2012) Heather J. Kulik et al.   JOURNAL OF PHYSICAL CHEMISTRY B

Putting the Pieces Together: Integrative Modeling Platform Software for Structure Determination of Macromolecular Assemblies

(2012) Daniel Russel et al.   PLOS BIOLOGY

Kinetic Network Study of the Diversity and Temperature Dependence of Trp-Cage Folding Pathways: Combining Transition Path Theory with Stochastic Simulations

(2011) Weihua Zheng et al.   JOURNAL OF PHYSICAL CHEMISTRY B

The resurgence of covalent drugs

(2011) Juswinder Singh et al.   NATURE REVIEWS DRUG DISCOVERY

Computational Design of Proteins Targeting the Conserved Stem Region of Influenza Hemagglutinin

(2011) S. J. Fleishman et al.   SCIENCE

The empirical valence bond model: theory and applications

(2011) Shina C. L. Kamerlin et al.   Wiley Interdisciplinary Reviews-Computational Molecular Science

Hydrogen exchange mass spectrometry for studying protein structure and dynamics

(2010) Lars Konermann et al.   CHEMICAL SOCIETY REVIEWS

Imaging cellular architecture with X-rays

(2010) Carolyn A Larabell et al.   CURRENT OPINION IN STRUCTURAL BIOLOGY

Dual-resolution molecular dynamics simulation of antimicrobials in biomembranes

(2010) M. Orsi et al.   Journal of the Royal Society Interface

Targeted Enzyme Prodrug Therapies

(2010) N. Schellmann et al.   MINI-REVIEWS IN MEDICINAL CHEMISTRY

Diffusion, Crowding & Protein Stability in a Dynamic Molecular Model of the Bacterial Cytoplasm

(2010) Sean R. McGuffee et al.   PLoS Computational Biology

Unraveling the Catalytic Pathway of Metalloenzyme Farnesyltransferase through QM/MM Computation

(2009) Ming-Hsun Ho et al.   Journal of Chemical Theory and Computation

Discovery Through the Computational Microscope

(2009) Eric H. Lee et al.   STRUCTURE

Fast Monte Carlo Simulation Methods for Biological Reaction-Diffusion Systems in Solution and on Surfaces

(2008) Rex A. Kerr et al.   SIAM JOURNAL ON SCIENTIFIC COMPUTING