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 treat the role of basic physical forces, key interactions, key residues, as well as the role of conformation, with an improved coarse-grained UNRES model, in several biological systems related to specific diseases. We will also continue the development of our UNRES model of nucleic acids (NARES-2P) and merge UNRES and NARES-2P into a viable package, which will be provided to the community. We will demonstrate how these aims can lead to valid predictions of structures and folding pathways of proteins, and protein-nucleic acid and protein-protein complexes. Our main focus will involve the application of this methodology to specific biological problems.
As pointed out in the Project Summary, the long-term objective of this research is to ascertain how protein conformation plays a role in various diseases. Examples of such diseases in which conformation plays a role are sickle cell anemia and amyloid diseases such as Alzheimer's and mad cow disease.
|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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