Breaking the size limit: efficient sampling of large-scale transition pathways and intermediate conformations in sub-mesoscopic protein complexes DOI
Laura Orellana, Domenico Scaramozzino, Byung Ho Lee

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: May 7, 2025

Abstract Protein conformational changes are the cornerstone of biological function. While conformers captured experimentally represent meta-stable states, pathways connecting them have been elusive for experiments and simulations alike. Nowadays, cryogenic Electron Microscopy is providing rich structural data on proteins trapped in different states increasingly large systems, but these out scope current computational methods, which usually exhibit an N2 dependence size. Based our previous eBDIMS algorithm, here we present eBDIMS2, extremely optimized version with quasi-linear size dependence, able to simulate a desktop computer exceptionally complex transitions megadalton protein assemblies, like rotary motion ATP synthases. Not only eBDIMS2 spontaneously visit experimental intermediates also overlap microsecond Molecular Dynamics requiring extensive supercomputing resources. By integrating Elastic Networks Brownian Dynamics, allows unprecedented exploration sub-mesoscopic previously inaccessible.

Language: Английский

Comprehensive Analysis of Density of States (DOS), UV-Visible, NMR Spectroscopy, and Molecular Electrostatic Potential (MEP) of RU-486 and its Derivatives (Ph, KOH, NO₂, OH) in Relation to Their Effects on Breast Cancer DOI
Hanifi Kebiroglu, Fermin Ak

Yüzüncü Yıl Üniversitesi Fen Bilimleri Enstitüsü Dergisi, Journal Year: 2025, Volume and Issue: 30(1), P. 46 - 60

Published: April 28, 2025

In this study, a comprehensive analysis was conducted on RU-486 (Mifepristone) and its derivatives (Ph, KOH, NO₂, OH), focusing their potential effectiveness against breast cancer. The included Density of States (DOS) optimization, UV-Visible spectroscopy, Nuclear Magnetic Resonance (NMR) Molecular Electrostatic Potential (MEP) mapping. electronic structures stabilities these molecules were examined through DOS, revealing how different functional groups influence properties. spectroscopy identified shifts in absorption maxima, which correspond to changes transitions due functionalization. NMR provided insights into the chemical environments specific nuclei, offering detailed information molecular geometry distribution. MEP mapped electrostatic across surfaces, pinpointing regions electrophilic nucleophilic reactivity. Collectively, analyses have enhanced understanding properties, reactivity, pharmaceutical applications cancer treatment.

Language: Английский

Citations

0
Breaking the size limit: efficient sampling of large-scale transition pathways and intermediate conformations in sub-mesoscopic protein complexes DOI
Laura Orellana, Domenico Scaramozzino, Byung Ho Lee

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: May 7, 2025

Abstract Protein conformational changes are the cornerstone of biological function. While conformers captured experimentally represent meta-stable states, pathways connecting them have been elusive for experiments and simulations alike. Nowadays, cryogenic Electron Microscopy is providing rich structural data on proteins trapped in different states increasingly large systems, but these out scope current computational methods, which usually exhibit an N2 dependence size. Based our previous eBDIMS algorithm, here we present eBDIMS2, extremely optimized version with quasi-linear size dependence, able to simulate a desktop computer exceptionally complex transitions megadalton protein assemblies, like rotary motion ATP synthases. Not only eBDIMS2 spontaneously visit experimental intermediates also overlap microsecond Molecular Dynamics requiring extensive supercomputing resources. By integrating Elastic Networks Brownian Dynamics, allows unprecedented exploration sub-mesoscopic previously inaccessible.

Language: Английский

Citations

0