AI Article Synopsis
Article Abstract
Although seeking to develop a general and accurate binding free energy calculation method for protein-protein and protein-ligand interactions has been a continuous effort for decades, only limited successes have been obtained so far. Here, we report the development of a metadynamics-based procedure that calculates Dissociation Free Energy (DFE) and its application to 19 non-congeneric protein-protein complexes and hundreds of protein-ligand complexes covering eight targets. We achieved very high correlations in comparison to experimental binding free energies for these diverse sets of systems, demonstrating the generality and accuracy of the method. Since structures of most proteins are available owing to the recent success of prediction by artificial intelligence, a general free energy method such as DFE, combined with other methods, can make structure-based drug design a widely viable and reliable solution to develop both traditional small molecule drugs and biologic drugs as well as PROTACS.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8821539 | PMC |
| http://dx.doi.org/10.1038/s41598-022-05875-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Conformational Space of 3-Chloropropionic Acid in Gas Phase Explored by Rotational Spectroscopy.
J Phys Chem A
December 2024
Departamento de Química Física y Química Inorgánica, Facultad de Ciencias─I.U. CINQUIMA, Paseo de Belén, 7, 47011 Valladolid, Spain.
The conformational space of 3-chloropropionic acid has been studied under the isolated conditions of a supersonic expansion using Stark-modulated free-jet absorption millimeter-wave and centimeter-wave chirped-pulse Fourier transform microwave spectroscopy techniques. The rotational spectra originating from the three most stable conformers including Cl and Cl isotopologues were observed in both experiments using helium expansion while a partial conformational relaxation involving skeletal rearrangements takes place in an argon expansion. The rotational parameters, geometries, and energy order were determined from the experiment, allowing a comparison with quantum chemical predictions.
View Article and Find Full Text PDFFree Energy-Based Refinement of DNA Force Field via Modification of Multiple Nonbonding Energy Terms.
J Chem Inf Model
December 2024
Department of Chemistry and Institute of Functional Materials, Pusan National University, Busan 46241, South Korea.
The amber-OL21 force field (ff) was developed to better describe noncanonical DNA, including Z-DNA. Despite its improvements for DNA simulations, this study found that OL21's scope of application was limited by embedded ff artifacts. In a benchmark set of seven DNA molecules, including two double-stranded DNAs transitioning between B- and Z-DNA and five single-stranded DNAs folding into mini-dumbbell or G-quadruplex structures, the free energy landscapes obtained using OL21 revealed several issues: Z-DNA was overly stabilized; misfolded states in mini-dumbbell DNAs were most stable; DNA GQ folding was consistently biased toward an antiparallel topology.
View Article and Find Full Text PDFMachine Learning Prediction of Physicochemical Properties in Lithium-Ion Battery Electrolytes With Active Learning Applied to Graph Neural Networks.
J Comput Chem
January 2025
Department of Chemistry, Birla Institute of Technology Mesra, Ranchi, India.
Accurate prediction of physicochemical properties, such as electronic energy, enthalpy, free energy, and average vibrational frequencies, is critical for optimizing lithium-ion battery (LIB) performance. Traditional methods like density functional theory (DFT) are computationally expensive and inefficient for large-scale screening. In this study, we apply active learning on top of graph neural networks (GNNs) to efficiently predict these properties.
View Article and Find Full Text PDFVDAC Solvation Free Energy Calculation by a Nonuniform Size Modified Poisson-Boltzmann Ion Channel Model.
J Comput Chem
January 2025
Department of Mathematical Sciences, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
Voltage-dependent anion channel (VDAC) is the primary conduit for regulated passage of ions and metabolites into and out of a mitochondrion. Calculating the solvation free energy for VDAC is crucial for understanding its stability, function, and interactions within the cellular environment. In this article, numerical schemes for computing the total solvation free energy for VDAC-comprising electrostatic, ideal gas, and excess free energies plus the nonpolar energy-are developed based on a nonuniform size modified Poisson-Boltzmann ion channel (nuSMPBIC) finite element solver along with tetrahedral meshes for VDAC proteins.
View Article and Find Full Text PDFRegulating Zn Deposition via Honeycomb-like Covalent Organic Frameworks for Stable Zn Metal Anodes.
ACS Appl Mater Interfaces
December 2024
Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an 710072, China.
The irreversible chemistry of the Zn anode, attributed to parasitic reactions and the growth of zinc dendrites, is the bottleneck in the commercialization of aqueous zinc-ion batteries. Herein, an efficient strategy via constructing an organic protective layer configured with a honeycomb-like globular-covalent organic framework (G-COF) was constructed to enhance the interfacial stability of Zn anodes. Theoretical analyses disclose that the methoxy and imine groups in G-COF have more negative adsorption energy and electrostatic potential distribution, favorable Zn adsorption, and diffusion.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!