Biological macromolecules energy landscapes with applications in biotechnology and in biomedicine

• Grant number: 16/19766-1
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2017
• End date: February 28, 2019
• Field of knowledge: Physical Sciences and Mathematics - Physics
• Principal Investigator: Vitor Barbanti Pereira Leite
• Grantee: Vitor Barbanti Pereira Leite
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

Understanding the relationships between structure, energetics and functional dynamics of proteins is one of the biggest challenges in molecular biophysics. The energy landscape approach has contributed significantly to the understanding of complex molecular systems such as protein folding problem, where minimalist and coarse-grained models have played a key role. Using coarse-grained models and statistical physics approaches, the problems addressed in this project can be divided into three groups:(1) Fundamental issues in the protein folding area. The topics covered are: understanding the diffusion coefficient in the representation of folding, study of the effects of frustration and non-native interactions in the folding process, and the visualization of the folding funnel. These methologies will be applied in the study of conformational transitions associated with protein functions.(2) Statistical approaches in bioinformatics and information processing, which complement the mechanistic computational approaches.(3) The tools developed will be integrated and applied in biotechnology and biomedicine problems. The technological application is on the study of enzymes involved in the generation of bioethanol in a theoretical-experimental collaboration. We use coarse-grained models in the study of the thermal stability of enzymes, focusing on 'in silico' stability optimization of enzymes and proposing site directed mutations to be tested experimentally. An immediate on going application aims at evaluating and optimizing enzyme cocktails used in the second generation bioethanol production. In biomedicine, these techniques have applications in various biological systems. We will investigate questions associated with Zika virus proteins, the estrogen receptor and on prospecting vaccines. (AU)

Scientific publications

(20)

(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)

CONTESSOTO, VINICIUS DE GODOI; RAMOS, FELIPE CARDOSO; DE MELO, RICARDO RODRIGUES; DE OLIVEIRA, VINICIUS MARTINS; SCARPASSA, JOSIANE ANIELE; DE SOUSA, AMANDA SILVA; ZANPHORLIN, LETICIA MARIA; SLADE, GABRIEL GOUVEA; PEREIRA LEITE, VITOR BARBANTI; RULLER, ROBERTO. lectrostatic interaction optimization improves catalytic rates and thermotolerance on xylanase. BIOPHYSICAL JOURNAL, v. 120, n. 11, p. 2172-2180, JUN 1 2021. (17/09662-7, 17/14253-9, 16/19766-1, 19/22540-3, 18/11614-3, 16/13998-8, 14/06862-7)

YANG, HUAN; BANDARKAR, PRASAD; HORNE, RANSOM; LEITE, VITOR B. P.; CHAHINE, JORGE; WHITFORD, PAUL C.. Diffusion of tRNA inside the ribosome is position-dependent. Journal of Chemical Physics, v. 151, n. 8, AUG 28 2019. (16/19766-1, 14/50739-5, 18/18668-1)

VINÍCIUS DE GODOI CONTESSOTO; ANTONIO BENTO DE OLIVEIRA JUNIOR; JORGE CHAHINE; RONALDO JUNIO DE OLIVEIRA; VITOR BARBANTI PEREIRA LEITE. Introdução ao problema de enovelamento de proteínas: uma abordagem utilizando modelos computacionais simplificados. Revista Brasileira de Ensino de Física, v. 40, n. 4, 2018-06-18. (16/13998-8, 17/09662-7, 14/06862-7, 16/19766-1)

DE OLIVEIRA, VINICIUS MARTINS; CONTESSOTO, VINICIUS DE GODOI; DA SILVA, FERNANDO BRUNO; ZAGO CAETANO, DANIEL LUCAS; DE CARVALHO, SIDNEY JURADO; PEREIRA LEITE, VITOR BARBANTI. Effects of pH and Salt Concentration on Stability of a Protein G Variant Using Coarse-Grained Models. BIOPHYSICAL JOURNAL, v. 114, n. 1, p. 65-75, JAN 9 2018. (13/13151-7, 16/19766-1, 16/13998-8, 17/09662-7, 14/06862-7)

CONTESSOTO, VINICIUS G.; DE OLIVEIRA, VINICIUS M.; FERNANDES, BRUNO R.; SLADE, GABRIEL G.; LEITE, VITOR B. P.. TKSA-MC: A web server for rational mutation through the optimization of protein charge interactions. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, v. 86, n. 11, p. 1184-1188, NOV 2018. (16/13998-8, 16/19766-1, 14/06862-7, 17/09662-7)

DE OLIVEIRA, VINICIUS M.; CAETANO, DANIEL L. Z.; DA SILVA, FERNANDO B.; MOURO, PAULO R.; DE OLIVEIRA, JR., ANTONIO B.; DE CARVALHO, SIDNEY J.; LEITE, VITOR B. P.. pH and Charged Mutations Modulate Cold Shock Protein Folding and Stability: A Constant pH Monte Carlo Study. JOURNAL OF CHEMICAL THEORY AND COMPUTATION, v. 16, n. 1, p. 765-772, JAN 2020. (16/19766-1, 18/18668-1, 18/11614-3, 18/01841-2)

OLIVEIRA, JR., ANTONIO B.; YANG, HUAN; WHITFORD, PAUL C.; LEITE, VITOR B. P.. Distinguishing Biomolecular Pathways and Metastable States. JOURNAL OF CHEMICAL THEORY AND COMPUTATION, v. 15, n. 11, p. 6482-6490, NOV 2019. (16/19766-1, 14/50739-5, 18/18668-1)

NGO, KHOA; DA SILVA, FERNANDO BRUNO; LEITE, VITOR B. P.; CONTESSOTO, VINICIUS G.; ONUCHIC, JOSE N.. Improving the Thermostability of Xylanase A from Bacillus subtilis by Combining Bioinformatics and Electrostatic Interactions Optimization. Journal of Physical Chemistry B, v. 125, n. 17, p. 4359-4367, MAY 6 2021. (16/19766-1, 19/22540-3, 14/06862-7, 16/13998-8, 17/09662-7)

DA SILVA, FERNANDO BRUNO; CONTESSOTO, VINICIUS G.; DE OLIVEIRA, VINICIUS M.; CLARKE, JANE; LEITE, VITOR B. P.. Non-Native Cooperative Interactions Modulate Protein Folding Rates. Journal of Physical Chemistry B, v. 122, n. 48, p. 10817-10824, DEC 6 2018. (16/19766-1, 16/13998-8, 17/09662-7, 14/06862-7, 18/11614-3)

BRUNI, ALINE THAIS; MARIZ DE CARVALHO, PEDRO OLIVEIRA; PINKE RODRIGUES, CAIO HENRIQUE; PEREIRA LEITE, VITOR BARBANTI. In silico methods in forensic science: Quantum chemistry and multivariate analysis applied to infrared spectra of new amphetamine- and cathinone-derived psychoactive substances. FORENSIC CHEMISTRY, v. 9, p. 21-34, JUN 2018. (16/19766-1)

CONTESSOTO, VINICIUS DE GODOI; RAMOS, FELIPE CARDOSO; DE MELO, RICARDO RODRIGUES; DE OLIVEIRA, VINICIUS MARTINS; SCARPASSA, JOSIANE ANIELE; DE SOUSA, AMANDA SILVA; ZANPHORLIN, LETICIA MARIA; SLADE, GABRIEL GOUVEA; PEREIRA LEITE, VITOR BARBANTI; RULLER, ROBERTO. Electrostatic interaction optimization improves catalytic rates and thermotolerance on xylanases. BIOPHYSICAL JOURNAL, v. 120, n. 11, p. 9-pg., 2021-06-01. (16/19766-1, 16/13998-8, 17/14253-9, 18/11614-3, 14/06862-7, 19/22540-3, 17/09662-7)

TAMBONIS, TIAGO; BOARETO, MARCELO; LEITE, VITOR B. P.. Differential Expression Analysis in RNA-seq Data Using a Geometric Approach. JOURNAL OF COMPUTATIONAL BIOLOGY, v. 25, n. 11, p. 1257-1265, NOV 2018. (16/19766-1, 14/06862-7)

DA SILVA, FERNANDO B.; DE OLIVEIRA, VINICIUS M.; SANCHES, MURILO N.; CONTESSOTO, VINICIUS G.; LEITE, VITOR B. P.. Rational Design of Chymotrypsin Inhibitor 2 by Optimizing Non-Native Interactions. JOURNAL OF CHEMICAL INFORMATION AND MODELING, v. 60, n. 2, p. 982-988, FEB 2020. (16/19766-1, 16/13998-8, 17/09662-7, 17/25130-5, 18/11614-3, 18/18668-1)

MOURO, PAULO R.; POVINELLI, ANA P. R.; LEITE, VITOR B. P.; CHAHINE, JORGE. Exploring Folding Aspects of Monomeric Superoxide Dismutase. Journal of Physical Chemistry B, v. 124, n. 4, p. 650-661, JAN 30 2020. (16/19766-1, 18/18668-1)

HERNANDEZ GONZALEZ, JORGE ENRIQUE; SALAS-SARDUY, EMIR; HERNANDEZ ALVAREZ, LILIAN; BARRETO GOMES, DIEGO ENRY; PASCUTTI, PEDRO GERALDO; OOSTENBRINK, CHRIS; LEITE, VITOR B. P.. In silico identification of noncompetitive inhibitors targeting an uncharacterized allosteric site of falcipain-2. Journal of Computer-Aided Molecular Design, v. 35, n. 10, p. 1067-1079, OCT 2021. (16/24587-9, 20/10214-1, 16/19766-1, 18/03911-8, 19/22540-3)

RODRIGUES, CAIO H. P.; LEITE, VITOR B. P.; BRUNI, ALINE T.. Can NMR spectroscopy discriminate between NPS amphetamines and cathinones? An evaluation by in silico studies and chemometrics. CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS, v. 210, MAR 15 2021. (19/22540-3, 16/19766-1)

CONTESSOTO, VINICIUS G.; FERREIRA, PAULO H. B.; CHAHINE, JORGE; LEITE, VITOR B. P.; OLIVEIRA, RONALDO J.. Small Neutral Crowding Solute Effects on Protein Folding Thermodynamic Stability and Kinetics. Journal of Physical Chemistry B, v. 125, n. 42, p. 11673-11686, OCT 28 2021. (16/13998-8, 19/22540-3, 16/19766-1)

SINHORINI, LUIZ F. C.; RODRIGUES, CAIO H. P.; LEITE, VITOR B. P.; BRUNI, ALINE T.. Synthetic fentanyls evaluation and characterization by infrared spectroscopy employing in silico methods. COMPUTATIONAL AND THEORETICAL CHEMISTRY, v. 1204, OCT 2021. (16/19766-1, 19/22540-3)

DE OLIVEIRA, VINICIUS M.; DIAS, MARIELI M. G.; AVELINO, THAYNA M.; VIDEIRA, NATALIA B.; DA SILVA, FERNANDO B.; DORATIOTO, TABATA R.; WHITFORD, PAUL C.; LEITE, VITOR B. P.; FIGUEIRA, ANA CAROLINA M.. pH and the Breast Cancer Recurrent Mutation D538G Affect the Process of Activation of Estrogen Receptor alpha. BIOCHEMISTRY, v. 61, n. 6, p. 9-pg., 2022-02-21. (18/11614-3, 19/10274-7, 14/50739-5, 16/02348-2, 19/22540-3, 16/19766-1, 19/14465-1)

RODRIGUES, CAIO H. P.; HERNANDEZ-GONZALEZ, JORGE E.; PEDRINA, NATALIA J.; LEITE, VITOR B. P.; BRUNI, ALINE T.. In silico Evaluation of Cucurbit[6]uril as a Potential Detector for Cocaine and Its Adulterants Lidocaine, Caffeine, and Procaine. Journal of the Brazilian Chemical Society, v. 32, n. 4, p. 800-810, APR 2021. (16/19766-1, 16/24587-9)