Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/d41586-025-00174-4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
High-throughput molecular simulations of SARS-CoV-2 receptor binding domain mutants quantify correlations between dynamic fluctuations and protein expression.
J Comput Chem
January 2025
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
Prediction of protein fitness from computational modeling is an area of active research in rational protein design. Here, we investigated whether protein fluctuations computed from molecular dynamics simulations can be used to predict the expression levels of SARS-CoV-2 receptor binding domain (RBD) mutants determined in the deep mutational scanning experiment of Starr et al. [Science (New York, N.
View Article and Find Full Text PDFCHARMM at 45: Enhancements in Accessibility, Functionality, and Speed.
J Phys Chem B
October 2024
Harvard University, Department of Chemistry and Chemical Biology, Cambridge, Massachusetts 02138, United States.
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 methods and applicability of CHARMM have also grown. This review summarizes major developments that occurred after 2009 when the last review of CHARMM was published.
View Article and Find Full Text PDFFree Energy Simulations of Receptor-Binding Domain Opening of the SARS-CoV-2 Spike Indicate a Barrierless Transition with Slow Conformational Motions.
J Phys Chem B
October 2023
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, United States.
Infection by sarbecoviruses begins with the attachment of the homotrimeric viral "spike" protein to the angiotensin-converting enzyme 2 receptor on the surface of mammalian cells. This requires one or more receptor-binding domains (RBDs) to be in the open (up) position. Here, we present the results of long molecular dynamics simulations with umbrella sampling (US) to compute a one-dimensional free energy profile of RBD opening/closing and the associated transition times.
View Article and Find Full Text PDFWater dynamics around T vs R of hemoglobin from local hydrophobicity analysis.
J Chem Phys
January 2023
Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138, USA.
The local hydration around tetrameric hemoglobin (Hb) in its T and R conformational substates is analyzed based on molecular dynamics simulations. Analysis of the local hydrophobicity (LH) for all residues at the αβ and αβ interfaces, responsible for the quaternary T → R transition, which is encoded in the Monod-Wyman-Changeux model, as well as comparison with earlier computations of the solvent accessible surface area, makes clear that the two quantities measure different aspects of hydration. Local hydrophobicity quantifies the presence and structure of water molecules at the interface, whereas "buried surface" reports on the available space for solvent.
View Article and Find Full Text PDFA Computational Framework for Determining the Breadth of Antibodies Against Highly Mutable Pathogens.
Methods Mol Biol
November 2022
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Highly mutable pathogens pose daunting challenges for antibody design. The usual criteria of high potency and specificity are often insufficient to design antibodies that provide long-lasting protection. This is due, in part, to the ability of the pathogen to rapidly acquire mutations that permit them to evade the designed antibodies.
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!