Bernard R. Brooks
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View article: Graph Neural Networks Model Based on Atomic Hybridization for Predicting Drug Targets
Graph Neural Networks Model Based on Atomic Hybridization for Predicting Drug Targets Open
Accurate prediction of half-maximal inhibitory concentration (IC 50 ) values is critical for accelerating drug discovery, yet traditional quantitative structure-activity relationship (QSAR) models often have limited ability to capture both…
View article: Self-Guided Molecular Simulation Methods
Self-Guided Molecular Simulation Methods Open
This work reviews self-guided (SG) molecular simulation methods and illustrates the characteristics and applications of these methods through several example simulations. The main characteristic of SG methods is that past motion in simulat…
View article: Characterizing the Ion-Conductive State of the <i>α</i> 7-Nicotinic Acetylcholine Receptor via Single-Channel Measurements and Molecular Dynamics Simulations
Characterizing the Ion-Conductive State of the <i>α</i> 7-Nicotinic Acetylcholine Receptor via Single-Channel Measurements and Molecular Dynamics Simulations Open
The α7-nicotinic acetylcholine receptor (α7-nAChR) is a cation-selective Cys-loop receptor involved in diverse physiological processes and is an important therapeutic target. Multiple cryo-EM structures of putative open states are now avai…
View article: Accurate Free Energy Calculation via Multiscale Simulations Driven by Hybrid Machine Learning and Molecular Mechanics Potentials
Accurate Free Energy Calculation via Multiscale Simulations Driven by Hybrid Machine Learning and Molecular Mechanics Potentials Open
This work develops a hybrid machine learning/molecular mechanics (ML/MM) interface integrated into the AMBER molecular simulation package. The resulting platform is highly versatile, accommodating several advanced machine learning interato…
View article: A parallel CUDA implementation of the Gauss–Legendre–spherical-<i>t</i> method for electrostatic interactions
A parallel CUDA implementation of the Gauss–Legendre–spherical-<i>t</i> method for electrostatic interactions Open
Computing electrostatic interactions remains the bottleneck of molecular dynamics (MD) simulations despite more than a century of effort in developing methods to accelerate the calculation. Previously, we have developed the spherical grids…
View article: Machine Learning-Driven Drug Repurposing for KRAS G12C and KRAS G12D Inhibition
Machine Learning-Driven Drug Repurposing for KRAS G12C and KRAS G12D Inhibition Open
KRAS is a predominant oncogenic driver across multiple cancers, long considered “undruggable” due to its high nucleotide affinity and lack of classical binding pockets. Although recent advances have led to covalent inhibitors like Sotorasi…
View article: Boltzmann Classifier: A Thermodynamic-Inspired Approach to Supervised Learning
Boltzmann Classifier: A Thermodynamic-Inspired Approach to Supervised Learning Open
We present the Boltzmann classifier, a novel distance based probabilistic classification algorithm inspired by the Boltzmann distribution. Unlike traditional classifiers that produce hard decisions or uncalibrated probabilities, the Boltzm…
View article: apoCHARMM: High-performance molecular dynamics simulations on GPUs for advanced simulation methods
apoCHARMM: High-performance molecular dynamics simulations on GPUs for advanced simulation methods Open
We present apoCHARMM, a high-performance molecular dynamics (MD) engine optimized for graphics processing unit (GPU) architectures, designed to accelerate the simulation of complex molecular systems. The distinctive features of apoCHARMM i…
View article: Predicting Iron–Sulfur Cluster Redox Potentials: A Simple Model Derived from Protein Structures
Predicting Iron–Sulfur Cluster Redox Potentials: A Simple Model Derived from Protein Structures Open
Iron-sulfur (Fe-S) clusters are critical cofactors in metalloproteins, essential for cellular processes such as energy production, DNA repair, enzymatic catalysis, and metabolic regulation. While Fe-S cluster functions are intimately linke…
View article: Leveraging-Induced Polarization for Drug Discovery: Efficient IC50 Prediction Using Minimal Features
Leveraging-Induced Polarization for Drug Discovery: Efficient IC50 Prediction Using Minimal Features Open
Here, we use the frequency of the atomic hybridizations (s, sp, sp2, and sp3) of each atom type (H, C, N, O, S, etc.) within a molecule to predict the IC50s of drug-like molecules, focusing on compounds targeting the Thrombin, Estrogen Rec…
View article: Accurate Free Energy Calculation via Multiscale Simulations Driven by Hybrid Machine Learning and Molecular Mechanics Potentials
Accurate Free Energy Calculation via Multiscale Simulations Driven by Hybrid Machine Learning and Molecular Mechanics Potentials Open
Our study focused on the implementation and testing of machine learning interatomic potentials (MLIPs) into the AMBER software suite. This implementation enables us to perform a novel type of molecular dynamics simulation utilizing the hyb…
View article: Self-Guided Molecular Simulation to Enhance Concerted Motion
Self-Guided Molecular Simulation to Enhance Concerted Motion Open
Self-guided (SG) molecular simulation methods, namely self-guided molecular dynamics (SGMD) and self-guided Langevin dynamics (SGLD), enhance conformational search by promoting low-frequency motion. A simple local time averaging scheme is …
View article: A Parallel CUDA Implementation of the Gauss-Legendre-Spherical-t Method for Electrostatic Interactions
A Parallel CUDA Implementation of the Gauss-Legendre-Spherical-t Method for Electrostatic Interactions Open
Computing electrostatic interactions remains the bottleneck of molecular dynamics (MD) simulations despite more than a century of effort in developing methods to accelerate the calculation. Previously we have developed the Spherical Grid a…
View article: Gauss-Legendre-Spherical-t (GLST) Cubature-Based Factorization of Long-Range Electrostatics in Simulations
Gauss-Legendre-Spherical-t (GLST) Cubature-Based Factorization of Long-Range Electrostatics in Simulations Open
We develop a highly parallelizable algorithm to calculate long-range electrostatic interactions named the Gauss-Legendre-Spherical-t (GLST) cubature method. Motivated by our recent spherical grid and treecode method, we utilize the Gauss-L…
View article: PKAD-R: Curated, Redesigned and Expanded Database of Experimental pKa Values in Proteins
PKAD-R: Curated, Redesigned and Expanded Database of Experimental pKa Values in Proteins Open
Understanding pKa values in ionizable protein residues is critical for understanding fundamental protein properties, such as structure, function and interactions. We present a new version of PKAD, named PKAD-R, which is a curated database …
View article: Accurate Free Energy Calculation via Multiscale Simulations Driven by Hybrid Machine Learning and Molecular Mechanics Potentials
Accurate Free Energy Calculation via Multiscale Simulations Driven by Hybrid Machine Learning and Molecular Mechanics Potentials Open
Our study focused on the implementation and testing of machine learning interatomic potentials (MLIPs) into the AMBER software suite. This implementation enables us to perform a novel type of molecular dynamics simulation utilizing the hyb…
View article: CHARMM at 45: Enhancements in Accessibility, Functionality, and Speed
CHARMM at 45: Enhancements in Accessibility, Functionality, and Speed Open
Since its inception nearly a half century ago, CHARMM has been playing a central role in computational biochemistry and biophysics. Commensurate with the developments in experimental research and advances in computer hardware, the range of…
View article: Mapping the Oxygens in the Oxygen-Evolving Complex of Photosystem II by Their Nucleophilicity Using Quantum Descriptors
Mapping the Oxygens in the Oxygen-Evolving Complex of Photosystem II by Their Nucleophilicity Using Quantum Descriptors Open
The oxygen-evolving complex (OEC) of Photosystem II catalyzes the water-splitting reaction using solar energy. Thus, understanding the reaction mechanism will inspire the design of biomimetic artificial catalysts that convert solar energy …
View article: MPI‐parallelization of the grid inhomogeneous solvation theory calculation
MPI‐parallelization of the grid inhomogeneous solvation theory calculation Open
The grid inhomogeneous solvation theory (GIST) method requires the often time‐consuming calculation of water–water and water‐solute energy on a grid. Previous efforts to speed up this calculation include using OpenMP, GPUs, and particle me…
View article: Ion channel selectivity through ion-modulated changes of selectivity filter p <i>K</i> <sub>a</sub> values
Ion channel selectivity through ion-modulated changes of selectivity filter p <i>K</i> <sub>a</sub> values Open
In bacterial voltage-gated sodium channels, the passage of ions through the pore is controlled by a selectivity filter (SF) composed of four glutamate residues. The mechanism of selectivity has been the subject of intense research, with su…
View article: Turning up the heat mimics allosteric signaling in imidazole-glycerol phosphate synthase
Turning up the heat mimics allosteric signaling in imidazole-glycerol phosphate synthase Open
Allosteric drugs have the potential to revolutionize biomedicine due to their enhanced selectivity and protection against overdosage. However, we need to better understand allosteric mechanisms in order to fully harness their potential in …
View article: Quantifying the effects of lossy compression on energies calculated from molecular dynamics trajectories
Quantifying the effects of lossy compression on energies calculated from molecular dynamics trajectories Open
Molecular dynamics (MD) simulations are now able to routinely reach timescales of microseconds and beyond. This has led to a corresponding increase in the amount of MD trajectory data that needs to be stored, particularly when those trajec…
View article: The Heat is On: Temperature Increase Mimics Allosteric Signaling in Imidazole-Glycerol Phosphate Synthase
The Heat is On: Temperature Increase Mimics Allosteric Signaling in Imidazole-Glycerol Phosphate Synthase Open
Allosteric drugs have the potential to revolutionize biomedicine due to their enhanced selectivity and protection against overdosage. However, we need to better understand allosteric mechanisms in order to fully harness their potential in …
View article: Efficient and Scalable Electrostatics via Spherical Grids and Treecode Summation
Efficient and Scalable Electrostatics via Spherical Grids and Treecode Summation Open
Evaluation of noncovalent electrostatic interactions is the dominant bottleneck in classical molecular dynamics simulations, and evaluation of Coulombic matrix elements similarly limits quantum mechanical self consistent field calculations…
View article: Deep attention based variational autoencoder for antimicrobial peptide discovery
Deep attention based variational autoencoder for antimicrobial peptide discovery Open
Antimicrobial peptides (AMPs) have been proposed as a potential solution against multiresistant pathogens. Designing novel AMPs requires exploration of a vast chemical space which makes it a challenging problem. Recently natural language p…