Robust protein–ligand interaction modeling through integrating physical laws and geometric knowledge for absolute binding free energy calculation

Qun Su, Jike Wang, Qiaolin Gou, Renling Hu, Linlong Jiang, Hui Zhang, Tianyue Wang, Yifei Liu, Chao Shen, Yu Kang, Chang-Yu Hsieh and Tingjun Hou

Chem. Sci., 2025, 16, 5043
DOI: 10.1039/D4SC07405J

Application of site-identification by ligand competitive saturation in computer-aided drug design

Himanshu Goel, Anthony Hazel, Wenbo Yu, Sunhwan Jo and Alexander D. MacKerell

New J. Chem., 2022, 46, 919
DOI: 10.1039/D1NJ04028F

Ranking mAb–excipient interactions in biologics formulations by NMR spectroscopy and computational approaches

Chunting Zhang, Steven T. Gossert, Jonathan Williams, Michael Little, Marilia Barros, Barton Dear, Bradley Falk, Ankit D. Kanthe, Robert Garmise, Luciano Mueller, Andrew Ilott and Anuji Abraham

mAbs, 2023, 15
DOI: 10.1080/19420862.2023.2212416

Accurate Free Energy Calculation via Multiscale Simulations Driven by Hybrid Machine Learning and Molecular Mechanics Potentials

Xujian Wang, Xiongwu Wu, Bernard R. Brooks and Junmei Wang

J. Chem. Theory Comput., 2025, 21, 6979
DOI: 10.1021/acs.jctc.5c00598

Bile Acids Are Potential Negative Allosteric Modulators of M1 Muscarinic Receptors

Wenbo Yu, Alexander D. MacKerell, David J. Weber and Jean-Pierre Raufman

Biomolecules, 2025, 15, 1326
DOI: 10.3390/biom15091326

Structure-Based Design of Potent Iminosugar Inhibitors of Endoplasmic Reticulum α-Glucosidase I with Anti-SARS-CoV-2 Activity

Sharanbasappa S. Karade, Evelyn J. Franco, Ana C. Rojas, Kaley C. Hanrahan, Alexander Kolesnikov, Wenbo Yu, Alexander D. MacKerell, Daniel C. Hill, David J. Weber, Ashley N. Brown, Anthony M. Treston and Roy A. Mariuzza

J. Med. Chem., 2023, 66, 2744
DOI: 10.1021/acs.jmedchem.2c01750

hERG Blockade Prediction by Combining Site Identification by Ligand Competitive Saturation and Physicochemical Properties

Himanshu Goel, Wenbo Yu and Alexander D. MacKerell

Chemistry, 2022, 4, 630
DOI: 10.3390/chemistry4030045

First-in-class mitogen-activated protein kinase (MAPK) p38α: MAPK-activated protein kinase 2 dual signal modulator with anti-inflammatory and endothelial-stabilizing properties

Mohan E. Tulapurkar, Kari Ann Shirey, Katerina Lugkey, Wendy Luo, Ritu Lal, Adam Galan, Omar Mahmoud, Nathaniel McClean, Kiruphagaran Thangaraju, Daniel Cericola, Daniel Lewis, William A. Murphy, Steven Fletcher, Alexander D. MacKerell, Stefanie N. Vogel, Paul Shapiro and Jeffrey D. Hasday

The Journal of Pharmacology and Experimental Therapeutics, 2025, 392, 100031
DOI: 10.1124/jpet.124.002281

Investigating the Interaction between Excipients and Monoclonal Antibodies PGT121 and N49P9.6-FR-LS: A Comprehensive Analysis

Xun Li, Asuka A. Orr, Mohammad M. Sajadi, Anthony L. DeVico, Daniel J. Deredge, Alexander D. MacKerell and Stephen W. Hoag

Mol. Pharmaceutics, 2025, 22, 1831
DOI: 10.1021/acs.molpharmaceut.4c00973

Systematic improvement of empirical energy functions in the era of machine learning

Mike Devereux, Eric D. Boittier and Markus Meuwly

J Comput Chem, 2024, 45, 1899
DOI: 10.1002/jcc.27367

Sampling the Grand Canonical Ensemble with Multisite λ Dynamics

Thanh T. Lai and Charles L. Brooks III

J. Phys. Chem. Lett., 2026, 17, 3852
DOI: 10.1021/acs.jpclett.6c00493

Potent and Selective Human Constitutive Androstane Receptor Activator DL5055 Facilitates Cyclophosphamide-Based Chemotherapies

Dongdong Liang, Linhao Li, Yong Ai, Zhihui Li, William D. Hedrich, Srilatha Sakamuru, Caitlin Lynch, Wenbo Yu, Ismael Watts-Ouattara, Scott Heyward, Menghang Xia, Alexander D. MacKerell, Hongbing Wang and Fengtian Xue

J. Med. Chem., 2025, 68, 7044
DOI: 10.1021/acs.jmedchem.4c02064

Integrated Covalent Drug Design Workflow Using Site Identification by Ligand Competitive Saturation

Wenbo Yu, David J. Weber and Alexander D. MacKerell

J. Chem. Theory Comput., 2023, 19, 3007
DOI: 10.1021/acs.jctc.3c00232

SILCS-RNA: Toward a Structure-Based Drug Design Approach for Targeting RNAs with Small Molecules

Abhishek A. Kognole, Anthony Hazel and Alexander D. MacKerell

J. Chem. Theory Comput., 2022, 18, 5672
DOI: 10.1021/acs.jctc.2c00381

Mitochondria-targeting artesunate-rhein conjugates: Linker-modulated cell-permeability, heme-affinity and anticancer activity

Dan-Dan Wang, Li He, Ming-Hui Qi, Hong-Yang Zhao, Ai-Xi Yu and Shi-Wen Huang

European Journal of Medicinal Chemistry, 2025, 282, 117100
DOI: 10.1016/j.ejmech.2024.117100

First-in-Class Potent, Dual HDAC6/Proteasome Inhibitors Lacking a Hydroxamic Acid Motif: Discovery of Novel Anti-Multiple Myeloma Agents

Alexandria M. Chan, Brandon D. Lowe, Andrea L. Cottingham, Daniel Van Eker, Asaminew H. Aytenfisu, Jace W. Jones, Alexander D. MacKerell, Ryan M. Pearson and Steven Fletcher

ACS Med. Chem. Lett., 2026, 17, 125
DOI: 10.1021/acsmedchemlett.5c00500

Targeting conserved domains of hypoxia-inducible factors for cancer therapy

Shaima Salman, Tina Y. Huang, Yousang Hwang, Anmol Kumar, Emmanuel Datan, Elizabeth E. Wicks, Ellen Cho, Sophia N. Lee, Chelsey Chen, Ying-Jie Peng, Dominic Dordai, Oscar Li, Daiana Drehmer, Yajing Lyu, Yongkang Yang, Walter Jackson, Nanduri R. Prabhakar, Alexander D. MacKerell and Gregg L. Semenza

Journal of Experimental Medicine, 2026, 223
DOI: 10.1084/jem.20251009

Enhancing SILCS-MC via GPU Acceleration and Ligand Conformational Optimization with Genetic and Parallel Tempering Algorithms

Mingtian Zhao, Wenbo Yu and Alexander D. MacKerell

J. Phys. Chem. B, 2024, 128, 7362
DOI: 10.1021/acs.jpcb.4c03045

Detection of Putative Ligand Dissociation Pathways in Proteins Using Site-Identification by Ligand Competitive Saturation

Wenbo Yu, David J. Weber and Alexander D. MacKerell

J. Chem. Inf. Model., 2025, 65, 3022
DOI: 10.1021/acs.jcim.4c01814

GPU‐specific algorithms for improved solute sampling in grand canonical Monte Carlo simulations

Mingtian Zhao, Abhishek A. Kognole, Sunhwan Jo, Aoxiang Tao, Anthony Hazel and Alexander D. MacKerell

J Comput Chem, 2023, 44, 1719
DOI: 10.1002/jcc.27121

Enlightenment the dynamic behavior of norbornene–modified ’click’ 4–arm polyethylene glycol hydrogel: Delving into framework properties and transport properties through molecular dynamics simulations

Rontu Das and Debashis Kundu

Computational Materials Science, 2025, 247, 113516
DOI: 10.1016/j.commatsci.2024.113516

Identifying and Assessing Putative Allosteric Sites and Modulators for CXCR4 Predicted through Network Modeling and Site Identification by Ligand Competitive Saturation

Tugce Inan, Robin Flinko, George K. Lewis, Alexander D. MacKerell and Ozge Kurkcuoglu

J. Phys. Chem. B, 2024, 128, 5157
DOI: 10.1021/acs.jpcb.4c00925

Site Identification by Ligand Competitive Saturation-Biologics Approach for Structure-Based Protein Charge Prediction

Asuka A. Orr, Aoxiang Tao, Olgun Guvench and Alexander D. MacKerell

Mol. Pharmaceutics, 2023, 20, 2600
DOI: 10.1021/acs.molpharmaceut.3c00064

GaSal-2: A Water-Soluble Antipseudomonal Agent Targeting the Extracellular Hemophore HasAp

Aziza Frank, Lucia Hwang, William T. Witt, Garrick Centola, Kieran Johnson, Yong Ai, Emel Sen-Kilic, Gage M. Pyles, Annalisa B. Huckaby, Catherine B. Blackwood, Sarah Jo Miller, S. Matthew Hudson, Kellie Hom, Wenbo Yu, Alexander D. MacKerell, Mariette Barbier, Angela Wilks and Fengtian Xue

ACS Infect. Dis., 2025, 11, 2287
DOI: 10.1021/acsinfecdis.5c00296

Molecular modeling in cardiovascular pharmacology: Current state of the art and perspectives

Jennifer Lagoutte-Renosi, Florentin Allemand, Christophe Ramseyer, Semen Yesylevskyy and Siamak Davani

Drug Discovery Today, 2022, 27, 985
DOI: 10.1016/j.drudis.2021.11.026

Discovery of non-peptide GLP-1r natural agonists for enhancing coronary safety in type 2 diabetes patients

Neda Shakour, Saeideh Hoseinpoor, Fatemeh Rajabian, Sabikeh G. Azimi, Mehrdad Iranshahi, Hojjat Sadeghi-Aliabadi and Farzin Hadizadeh

Journal of Biomolecular Structure and Dynamics, 2025, 43, 3508
DOI: 10.1080/07391102.2023.2298734

Computational Modeling of PROTAC Ternary Complexes as Ensembles Using SILCS-xTAC

Erik B. Nordquist, Mingtian Zhao, Wenbo Yu and Alexander D. MacKerell Jr

J. Chem. Inf. Model., 2026, 66, 701
DOI: 10.1021/acs.jcim.5c02045

Solvent optimization for caffeine and tannic acid extraction from Guarana seed: Insights from molecular dynamics simulations

Abhinav Tidke, Rontu Das, Uday S. Annapure and Debashis Kundu

Journal of Molecular Liquids, 2024, 416, 126462
DOI: 10.1016/j.molliq.2024.126462

Modeling Ligand Binding Site Water Networks with Site Identification by Ligand Competitive Saturation: Impact on Ligand Binding Orientations and Relative Binding Affinities

Anmol Kumar, Himanshu Goel, Wenbo Yu, Mingtian Zhao and Alexander D. MacKerell

J. Chem. Theory Comput., 2024, 20, 11032
DOI: 10.1021/acs.jctc.4c01165

Combining SILCS and Artificial Intelligence for High-Throughput Prediction of the Passive Permeability of Drug Molecules

Poonam Pandey and Alexander D. MacKerell

J. Chem. Inf. Model., 2023, 63, 5903
DOI: 10.1021/acs.jcim.3c00514

Vaccinomics Approach for Multi-Epitope Vaccine Design against Group A Rotavirus Using VP4 and VP7 Proteins

Muhammad Usman, Aaima Ayub, Sabahat Habib, Muhammad Rana, Zaira Rehman, Ali Zohaib, Syed Jamal, Arun Jaiswal, Bruno Andrade, Vasco de Carvalho Azevedo, Muhammad Faheem and Aneela Javed

Vaccines, 2023, 11, 726
DOI: 10.3390/vaccines11040726

Non-β Lactam Inhibitors of the Serine β-Lactamase blaCTX-M15 in Drug-Resistant Salmonella typhi

Faisal Ahmad, Nousheen Parvaiz, Alexander D. MacKerell and Syed Sikander Azam

J. Chem. Inf. Model., 2023, 63, 6681
DOI: 10.1021/acs.jcim.3c00780

Extracting Atomic Contributions to Binding Free Energy Using Molecular Dynamics Simulations with Mixed Solvents (MDmix)

Daniel Alvarez-Garcia, Peter Schmidtke, Elena Cubero and Xavier Barril

CDDT, 2022, 19
DOI: 10.2174/1570163819666211223162829

Combined Physics- and Machine-Learning-Based Method to Identify Druggable Binding Sites Using SILCS-Hotspots

Erik B. Nordquist, Mingtian Zhao, Anmol Kumar and Alexander D. MacKerell

J. Chem. Inf. Model., 2024, 64, 7743
DOI: 10.1021/acs.jcim.4c01189

Evolutionary divergence in the conformational landscapes of tyrosine vs serine/threonine kinases

Joan Gizzio, Abhishek Thakur, Allan Haldane and Ronald M Levy

eLife, 2022, 11
DOI: 10.7554/eLife.83368

High-Throughput Ligand Dissociation Kinetics Predictions Using Site Identification by Ligand Competitive Saturation

Wenbo Yu, Shashi Kumar, Mingtian Zhao, David J. Weber and Alexander D. MacKerell

J. Chem. Theory Comput., 2025, 21, 4964
DOI: 10.1021/acs.jctc.5c00265

Molecular guidelines for promising antimicrobial agents

Mateusz Rzycki, Marta Gładysiewicz-Kudrawiec and Sebastian Kraszewski

Sci Rep, 2024, 14
DOI: 10.1038/s41598-024-55418-6