Advanced search
Start date
Betweenand
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

MD simulations and multivariate studies for modeling the antileishmanial activity of peptides

Full text
Author(s):
Rodrigues Guerra, Mirian Elisa ; Fadel, Valmir ; Maltarollo, Vinicius Goncalves ; Baldissera, Gisele ; Honorio, Kathia Maria ; Ruggiero, Jose Roberto ; dos Santos Cabrera, Marcia Perez
Total Authors: 7
Document type: Journal article
Source: CHEMICAL BIOLOGY & DRUG DESIGN; v. 90, n. 4, p. 501-510, OCT 2017.
Web of Science Citations: 4
Abstract

Leishmaniasis, a protozoan-caused disease, requires alternative treatments with minimized side-effects and less prone to resistance development. Antimicrobial peptides represent a possible choice to be developed. We report on the prospection of structural parameters of 23 helical antimicrobial and leishmanicidal peptides as a tool formodeling and predicting the activity of new peptides. This investigation is based on molecular dynamic simulations (MD) in mimetic membrane environment, as most of these peptides share the feature of interacting with phospholipid bilayers. To overcome the lack of experimental data on peptides' structures, we started simulations from designed 100% -helices. This procedure was validated through comparisons with NMR data and the determination of the structure of Decoralin-amide. From physicochemical features and MD results, descriptors were raised and statistically related to the minimum inhibitory concentration against Leishmania by the multivariate data analysis technique. This statistical procedure confirmed five descriptors combined by different loadings in five principal components. The leishmanicidal activity depends on peptides' charge, backbone solvation, volume, and solvent-accessible surface area. The generated model possesses good predictability (q(2)=0.715, r(2)=0.898) and is indicative for the most and the least active peptides. This is a novel theoretical path for structure-activity studies combining computational methods that identify and prioritize the promising peptide candidates. (AU)

FAPESP's process: 06/57122-7 - Searching for lead compounds for rational development of new drugs and pesticides through bioprospecting in Brazilian arthropods
Grantee:Mario Sergio Palma
Support type: BIOTA-FAPESP Program - Thematic Grants
FAPESP's process: 14/08372-7 - Peptide and chitosan conjugates with pharmacological potential: synthesis, prospecting of activity in membrane mimetic systems, and evaluation in cells
Grantee:Marcia Perez dos Santos Cabrera
Support type: Scholarships in Brazil - Young Researchers
FAPESP's process: 12/24259-0 - Peptide and chitosan conjugates with pharmacological potential: synthesis, prospecting of activity in membrane mimetic systems, and evaluation in cells
Grantee:Marcia Perez dos Santos Cabrera
Support type: Research Grants - Young Investigators Grants