3/31/2023 0 Comments Protein backboneThis parameter set, which we denote ff99SB, achieves a better balance of secondary structure elements as judged by improved distribution of backbone dihedrals for glycine and alanine with respect to PDB survey data. The new parameters for backbone dihedrals replace those in the existing ff99 force field. Dihedral term parameters are based on fitting the energies of multiple conformations of glycine and alanine tetrapeptides from high level ab initio quantum mechanical calculations. We report here an effort to improve the φ/ψ dihedral terms in the ff99 energy function. This led to parameter sets that provide unreasonable conformational preferences for glycine. In addition, the approach used in most of these studies neglected to account for the existence in Amber of two sets of backbone φ/ψ dihedral terms. We show that several of these continue to suffer from inadequate balance between different secondary structure elements. This led to a number of attempts to improve these parameters, resulting in a variety of “Amber” force fields and significant difficulty in determining which should be used for a particular application. After a decade of extensive use and testing, limitations in this force field, such as over-stabilization of α-helices, were reported by us and other researchers. Evidence for an Ordering Transition near 120 K in an Intrinsically Disordered Protein, Casein.The ff94 force field that is commonly associated with the Amber simulation package is one of the most widely used parameter sets for biomolecular simulation. Probing Small-Angle Molecular Motions with EPR Spectroscopy: Dynamical Transition and Molecular Packing in Disordered Solids. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics 2022, 1870 A unifying framework for amyloid-mediated membrane damage: The lipid-chaperone hypothesis. Carmelo Tempra, Federica Scollo, Martina Pannuzzo, Fabio Lolicato, Carmelo La Rosa.Spectroscopic investigation of biomolecular dynamics using light scattering methods. The Journal of Physical Chemistry B 2021, 125 Thermodynamic Compensation in Peptides Following Liquid–Liquid Phase Separation. Effects of Glycine on the Local Conformation and Internal Backbone Dynamics of Polypeptides. The Journal of Physical Chemistry B 2022, 126 Conformational Characteristics and Phase Behavior of Intrinsically Disordered Proteins─Where Physical Chemistry Meets Biology. Sequence Context and Complex Hofmeister Salt Interactions Dictate Phase Separation Propensity of Resilin-like Polypeptides. Effects of Conformational Constraint on Peptide Solubility Limits. Lastly, we discuss changes in the dynamics of side chains and order–disorder transitions of the protein backbone as two modes or realizations of “entropic reservoirs” capable of tuning coupled thermodynamic processes. Particular attention is paid to the results of computational studies, which, through thermodynamic decomposition and dissection of molecular interactions, can provide valuable mechanistic insight and testable hypotheses to guide further solution experiments. In this review, we survey these properties through the conceptual lenses of solubility and conformational populations and in the context of protein-disorder mediated phenomena (e.g., phase separation, order–disorder transitions, allostery). The versatile physicochemical properties of the protein backbone must accommodate structural disorder, order, and transitions between these states. While function, composition, and structural properties largely differ, these two classes of protein are built upon the same scaffold, namely, the protein backbone. It is enticing and oftentimes practical to divide the proteome into structured and unstructured, or disordered, proteins. Rather, spectra of functionally competent, structurally disordered states have been uncovered requiring canonical paradigms in molecular biology to be revisited or reimagined. Over the last two decades it has become clear that well-defined structure is not a requisite for proteins to properly function.
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