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27 Publications visible to you, out of a total of 27
Brownian dynamics simulations of biomolecular diffusional association processes

Abstract (Expand)

Abstract Brownian dynamics (BD) is a computational method to simulate molecular diffusion processes. Although the BD method has been developed over several decades and is well established, new …d is well established, new methodological developments are improving its accuracy, widening its scope, and increasing its application. In biological applications, BD is used to investigate the diffusive behavior of molecules subject to forces due to intermolecular interactions or interactions with material surfaces. BD can be used to compute rate constants for diffusional association, generate structures of encounter complexes for molecular binding partners, and examine the transport properties of geometrically complex molecules. Often, a series of simulations is performed, for example, for different protein mutants or environmental conditions, so that the effects of the changes on diffusional properties can be estimated. While biomolecules are commonly described at atomic resolution and internal molecular motions are typically neglected, coarse‐graining and the treatment of conformational flexibility are increasingly employed. Software packages for BD simulations of biomolecules are growing in capabilities, with several new packages providing novel features that expand the range of questions that can be addressed. These advances, when used in concert with experiment or other simulation methods, such as molecular dynamics, open new opportunities for application to biochemical and biological systems. Here, we review some of the latest developments in the theory, methods, software, and applications of BD simulations to study biomolecular diffusional association processes and provide a perspective on their future use and application to outstanding challenges in biology, bioengineering, and biomedicine. This article is categorized under: Structure and Mechanism > Computational Biochemistry and Biophysics Molecular and Statistical Mechanics > Molecular Dynamics and Monte‐Carlo Methods Software > Simulation Methods

Authors: Abraham Muñiz‐Chicharro, Lane W. Votapka, Rommie E. Amaro, Rebecca C. Wade

Date Published: 1st May 2023

Publication Type: Journal

Scaling Protein–Water Interactions in the Martini 3 Coarse-Grained Force Field to Simulate Transmembrane Helix Dimers in Different Lipid Environments

Abstract

Not specified

Authors: Ainara Claveras Cabezudo, Christina Athanasiou, Alexandros Tsengenes, Rebecca C. Wade

Date Published: 11th Apr 2023

Publication Type: Journal

Glycosaminoglycans: What Remains To Be Deciphered?

Abstract

Not specified

Authors: Serge Perez, Olga Makshakova, Jesus Angulo, Emiliano Bedini, Antonella Bisio, Jose Luis de Paz, Elisa Fadda, Marco Guerrini, Michal Hricovini, Milos Hricovini, Frederique Lisacek, Pedro M. Nieto, Kevin Pagel, Giulia Pairardi, Ralf Richter, Sergey A. Samsonov, Romain A. Vivès, Dragana Nikitovic, Sylvie Ricard Blum

Date Published: 27th Mar 2023

Publication Type: Journal

An artificial neural network model to predict structure-based protein–protein free energy of binding from Rosetta-calculated properties

Abstract

An artificial neural network protocol to compute protein–protein free energy of binding.

Authors: Matheus V. F. Ferraz, José C. S. Neto, Roberto D. Lins, Erico S. Teixeira

Date Published: 8th Mar 2023

Publication Type: Journal

Enhanced sampling simulations and machine learning to address infectious diseases

Abstract

Not specified

Author: Matheus Ferraz

Date Published: 2023

Publication Type: Doctoral Thesis

Computational Investigation of the Structure Kinetics Relationship of Small-Molecule Compounds Binding the Histamine-1-Receptor

Abstract

Not specified

Author: Melanie Kaeser

Date Published: 9th Dec 2022

Publication Type: Master's Thesis

Destabilizers of the thymidylate synthase homodimer accelerate its proteasomal degradation and inhibit cancer growth.

Abstract (Expand)

Drugs that target human thymidylate synthase (hTS), a dimeric enzyme, are widely used in anticancer therapy. However, treatment with classical substrate-site-directed TS inhibitors induces over-expression … of this protein and development of drug resistance. We thus pursued an alternative strategy that led us to the discovery of TS-dimer destabilizers. These compounds bind at the monomer-monomer interface and shift the dimerization equilibrium of both the recombinant and the intracellular protein toward the inactive monomers. A structural, spectroscopic, and kinetic investigation has provided evidence and quantitative information on the effects of the interaction of these small molecules with hTS. Focusing on the best among them, E7, we have shown that it inhibits hTS in cancer cells and accelerates its proteasomal degradation, thus causing a decrease in the enzyme intracellular level. E7 also showed a superior anticancer profile to fluorouracil in a mouse model of human pancreatic and ovarian cancer. Thus, over sixty years after the discovery of the first TS prodrug inhibitor, fluorouracil, E7 breaks the link between TS inhibition and enhanced expression in response, providing a strategy to fight drug-resistant cancers.

Authors: L. Costantino, S. Ferrari, M. Santucci, O. M. H. Salo-Ahen, E. Carosati, S. Franchini, A. Lauriola, C. Pozzi, M. Trande, G. Gozzi, P. Saxena, G. Cannazza, L. Losi, D. Cardinale, A. Venturelli, A. Quotadamo, P. Linciano, L. Tagliazucchi, M. G. Moschella, R. Guerrini, S. Pacifico, R. Luciani, F. Genovese, S. Henrich, S. Alboni, N. Santarem, A. da Silva Cordeiro, E. Giovannetti, G. J. Peters, P. Pinton, A. Rimessi, G. Cruciani, R. M. Stroud, R. C. Wade, S. Mangani, G. Marverti, D. D'Arca, G. Ponterini, M. P. Costi

Date Published: 7th Dec 2022

Publication Type: Journal

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