Our long-term objective is to ascertain how protein conformation plays a role in biological function and in various diseases.
Our specific aims are to combine a new physics-based method for homology searching, the Property Factor Method (PFM), with our coarse- grained UNRES potential energy function, and with all-atom potentials, to model several biological systems related to specific diseases. We will also continue the development of the PFM approach, with a view to improving the success of homology modeling. We will demonstrate how these aims can lead to valid predictions of structures and folding pathways of proteins. Our main focus will involve the application of this methodology to specific biological problems.

Public Health Relevance

The long-term objective of the proposed research is to ascertain how protein conformation plays a role in various diseases. Examples of diseases in which conformation plays a role include sickle cell anemia and such amyloid diseases as Alzheimer?s and mad cow disease.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Macromolecular Structure and Function D Study Section (MSFD)
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Wehrle, Janna P
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Cornell University
Schools of Arts and Sciences
United States
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Cote, Yoann; Delarue, Patrice; Scheraga, Harold A et al. (2018) From a Highly Disordered to a Metastable State: Uncovering Insights of ?-Synuclein. ACS Chem Neurosci 9:1051-1065
Vorobjev, Yury N; Scheraga, Harold A; Vila, Jorge A (2018) A comprehensive analysis of the computed tautomer fractions of the imidazole ring of histidines in Loligo vulgaris. J Biomol Struct Dyn 36:3094-3105
Grassein, Paul; Delarue, Patrice; Scheraga, Harold A et al. (2018) Statistical Model To Decipher Protein Folding/Unfolding at a Local Scale. J Phys Chem B 122:3540-3549
Solé-Domènech, Santiago; Rojas, Ana V; Maisuradze, Gia G et al. (2018) Lysosomal enzyme tripeptidyl peptidase 1 destabilizes fibrillar A? by multiple endoproteolytic cleavages within the ?-sheet domain. Proc Natl Acad Sci U S A 115:1493-1498
Vorobjev, Yury N; Scheraga, Harold A; Vila, Jorge A (2018) Coupled molecular dynamics and continuum electrostatic method to compute the ionization pKa's of proteins as a function of pH. Test on a large set of proteins. J Biomol Struct Dyn 36:561-574
Keasar, Chen; McGuffin, Liam J; Wallner, Björn et al. (2018) An analysis and evaluation of the WeFold collaborative for protein structure prediction and its pipelines in CASP11 and CASP12. Sci Rep 8:9939
Rojas, Ana; Maisuradze, Nika; Kachlishvili, Khatuna et al. (2017) Elucidating Important Sites and the Mechanism for Amyloid Fibril Formation by Coarse-Grained Molecular Dynamics. ACS Chem Neurosci 8:201-209
He, Yi; Maisuradze, Gia G; Yin, Yanping et al. (2017) Sequence-, structure-, and dynamics-based comparisons of structurally homologous CheY-like proteins. Proc Natl Acad Sci U S A 114:1578-1583
Makowski, Mariusz; Liwo, Adam; Scheraga, Harold A (2017) Simple Physics-Based Analytical Formulas for the Potentials of Mean Force of the Interaction of Amino Acid Side Chains in Water. VII. Charged-Hydrophobic/Polar and Polar-Hydrophobic/Polar Side Chains. J Phys Chem B 121:379-390
Vila, Jorge A; Scheraga, Harold A (2017) Limiting Values of the one-bond C-H Spin-Spin Coupling Constants of the Imidazole Ring of Histidine at High-pH. J Mol Struct 1134:576-581

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