A multi-resolution approach to cation-induced polymorphism of lipopolysaccharide aggregates

• Grant number: 21/04283-3
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2021
• End date: July 31, 2024
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Thereza Amélia Soares da Silva
• Grantee: Thereza Amélia Soares da Silva
• Host Institution: Instituto de Física (IF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 22/13855-3 - A Multi-Resolution Approach to Cation-induced Polymorphism of Lipopolysaccharide Aggregates, BP.TT

Abstract

Lipopolysaccharides (LPS) are the major components of the outer membrane (OM) of Gram-negative bacteria, a highly effective permeability barrier against antibiotics and the host cell defense system. Critical physical-chemical properties of the OM (e.g. stability, low permeability, hydration) are modulated by the hydration dynamics of metals coordinating phosphate groups from distinct LPS molecules. The present proposal aims to establish the role of a series of alkali and alkaline earth metals on the stability and structural transitions of LPS aggregates via a multi-resolution computational approach. At the highest resolution, it will make use of QM/MM methodologies to determine electronic properties critical for the accurate description of cation hydration dynamics. These properties will be used to refine the classical description of cations in a previously developed force field extension for glycolipids and validated via atomistic simulations of the LPS aggregates containing a variety of mono- and divalent cations. At the lowest resolution, these MD-derived structural ensembles will serve as reference systems for the development of an accurate coarse-grain representation of LPS and cations compatible with the hybrid particle-field (hPF) method. This approach will allow to assess of the accuracy of additive potentials for use in classical MD simulations and to develop accurate hPF-compatible models that can sample time- and spatial scales inaccessible to atomistic representations. The present proposal will provide the computational scaffold for a comprehensive characterization of the microscopic mechanism underlying cation-induced structural transitions in glycolipid aggregates. It is anticipated that this research outcome will be of relevance for the development of new antimicrobials that target the cell wall of Gram-negative bacteria. This multidisciplinary project will be carried out as an extension of previously established international collaborations. (AU)

Scientific publications

(7)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SANTOS, DENYS E. S.; COUTINHO, KALINE; SOARES, THEREZA A.. Surface Assessment via Grid Evaluation (SuAVE) for Every Surface Curvature and Cavity Shape. JOURNAL OF CHEMICAL INFORMATION AND MODELING, v. N/A, p. 12-pg., 2022-08-10. (21/04283-3, 21/09016-3)

SANTOS, DENYS E. S.; DE NICOLA, ANTONIO; DOS SANTOS, VINICIUS F.; MILANO, GIUSEPPE; SOARES, THEREZA A. A.. Exploring the Molecular Dynamics of a Lipid-A Vesicle at the Atom Level: Morphology and Permeation Mechanism. Journal of Physical Chemistry B, v. 127, n. 30, p. 9-pg., 2023-07-19. (21/04283-3)

CASCELLA, MICHELE; SOARES, THEREZA A.. Bias Amplification in Gender, Gender Identity, and Geographical Affiliation. JOURNAL OF CHEMICAL INFORMATION AND MODELING, v. 62, n. 24, p. 5-pg., 2022-05-19. (21/04283-3)

CARRER, MANUEL; NIELSEN, JOSEFINE EILSO; CEZAR, HENRIQUE MUSSELI; LUND, REIDAR; CASCELLA, MICHELE; SOARES, THEREZA A.. Accelerating Lipid Flip-Flop at Low Concentrations: A General Mechanism for Membrane Binding Peptides. Journal of Physical Chemistry Letters, v. 14, n. 31, p. 6-pg., 2023-07-31. (21/04283-3)

SOARES, THEREZA A.; NUNES-ALVES, ARIANE; MAZZOLARI, ANGELICA; RUGGIU, FIORELLA; WEI, GUO-WEI; MERZ, KENNETH. The (Re)-Evolution of Quantitative Structure-Activity Relationship (QSAR) Studies Propelled by the Surge of Machine Learning Methods. JOURNAL OF CHEMICAL INFORMATION AND MODELING, v. 62, n. 22, p. 4-pg., 2022-11-28. (21/04283-3)

SANTOS, DENYS E. S.; COUTINHO, KALINE; SOARES, THEREZA A.. Surface Assessment via Grid Evaluation (SuAVE) for Every Surface Curvature and Cavity Shape. JOURNAL OF CHEMICAL INFORMATION AND MODELING, v. 62, n. 19, p. 12-pg., 2022-10-10. (21/09016-3, 21/04283-3)

VENDITE, ALEXSANDER C.; SOARES, THEREZA A. .; COUTINHO, KALINE. The Effect of Surface Composition on the Selective Capture of Atmospheric CO2 by ZIF Nanoparticles: The Case of ZIF-8. JOURNAL OF CHEMICAL INFORMATION AND MODELING, v. 62, n. 24, p. 14-pg., 2022-09-23. (21/09016-3, 19/08465-9, 21/04283-3, 17/11631-2)