Landscape of intrinsically disordered proteins in mental disorder diseases.

Disrupted genes linked to mental disorders sometimes exhibit characteristics of Intrinsically Disordered Proteins (IDPs). However, few studies have comprehensively explored the functional associations between protein disorder properties and different psychiatric disorders. In this study, we collected disrupted proteins for seven mental diseases (MDD, SCZ, BP, ID, AD, ADHD, ASD) and a control dataset from normal brains.

Intrinsic Disorder and Other Malleable Arsenals of Evolved Protein Multifunctionality.

Microscopic evolution at the functional biomolecular level is an ongoing process. Leveraging functional and high-throughput assays, along with computational data mining, has led to a remarkable expansion of our understanding of multifunctional protein (and gene) families over the past few decades. Various molecular and intermolecular mechanisms are now known that collectively meet the cumulative multifunctional demands in higher organisms along an evolutionary path.

Combining Complementarity and Binding Energetics in the Assessment of Protein Interactions: EnCPdock-A Practical Manual.

The combined effect of shape and electrostatic complementarities (Sc, EC) at the interface of the interacting protein partners (PPI) serves as the physical basis for such associations and is a strong determinant of their binding energetics. EnCPdock (https://www.scinetmol.

Modified host defence peptide GF19 slows TNT-mediated spread of corneal herpes simplex virus serotype I infection.

Corneal HSV-1 infections are a leading cause of infectious blindness globally by triggering tissue damage due to the intense inflammation. HSV-1 infections are treated mainly with antiviral drugs that clear the infections but are inefficient as prophylactics. The body produces innate cationic host defence peptides (cHDP), such as the cathelicidin LL37.

EnCPdock: a web-interface for direct conjoint comparative analyses of complementarity and binding energetics in inter-protein associations.

Context: Protein-protein interaction (PPI) is a key component linked to virtually all cellular processes. Be it an enzyme catalysis ('classic type functions' of proteins) or a signal transduction ('non-classic'), proteins generally function involving stable or quasi-stable multi-protein associations. The physical basis for such associations is inherent in the combined effect of shape and electrostatic complementarities (Sc, EC) of the interacting protein partners at their interface, which provides indirect probabilistic estimates of the stability and affinity of the interaction.

BRANEart: Identify Stability Strength and Weakness Regions in Membrane Proteins.

Understanding the role of stability strengths and weaknesses in proteins is a key objective for rationalizing their dynamical and functional properties such as conformational changes, catalytic activity, and protein-protein and protein-ligand interactions. We present BRANEart, a new, fast and accurate method to evaluate the per-residue contributions to the overall stability of membrane proteins. It is based on an extended set of recently introduced statistical potentials derived from membrane protein structures, which better describe the stability properties of this class of proteins than standard potentials derived from globular proteins.

Capturing a Crucial 'Disorder-to-Order Transition' at the Heart of the Coronavirus Molecular Pathology-Triggered by Highly Persistent, Interchangeable Salt-Bridges.

The COVID-19 origin debate has greatly been influenced by genome comparison studies of late, revealing the emergence of the Furin-like cleavage site at the S1/S2 junction of the SARS-CoV-2 Spike (FLCS) containing its motif, absent in other related respiratory viruses. Being the rate-limiting (i.e.

Can the jigsaw puzzle model of protein folding re-assemble a hydrophobic core?

According to the "jigsaw puzzle" model of protein folding, the isomorphism between sequence and structure is substantially determined by the specific geometry of side-chain interactions, within the protein interior. In this work, we have attempted to predict the hydrophobic core of cyclophilin (LdCyp) from Leishmania donovani, utilizing a surface complementarity function, which selects for high goodness of fit between hydrophobic side-chain surfaces, rather in the manner of assembling a three-dimensional jigsaw puzzle. The computational core prediction method implemented here has been tried on two distinct scenarios, on the LdCyp polypeptide chain with native non-core residues and all core residues initially set to alanine, on a poly-glycine polypeptide chain.

Special Issue on 'Coronavirus: Vaccines and Other Therapeutics' (2020-2021).

As is well known, the emergence of SARS-CoV-2 ever since late 2019 [...

Plausible blockers of Spike RBD in SARS-CoV2-molecular design and underlying interaction dynamics from high-level structural descriptors.

COVID-19 is characterized by an unprecedented abrupt increase in the viral transmission rate (SARS-CoV-2) relative to its pandemic evolutionary ancestor, SARS-CoV (2003). The complex molecular cascade of events related to the viral pathogenicity is triggered by the Spike protein upon interacting with the ACE2 receptor on human lung cells through its receptor binding domain (RBD). One potential therapeutic strategy to combat COVID-19 could thus be limiting the infection by blocking this key interaction.

Criticality in the conformational phase transition among self-similar groups in intrinsically disordered proteins: Probed by salt-bridge dynamics.

Intrinsically disordered proteins (IDP) serve as one of the key components in the global proteome. In contrast to globular proteins, they harbor an enormous amount of physical flexibility enforcing them to be retained in conformational ensembles rather than stable folds. Previous studies in an aligned direction have revealed the importance of transient dynamical phenomena like that of salt-bridge formation in IDPs to support their physical flexibility and have further highlighted their functional relevance.

Inner-View of Nanomaterial Incited Protein Conformational Changes: Insights into Designable Interaction.

Nanoparticle bioreactivity critically depends upon interaction between proteins and nanomaterials (NM). The formation of the "protein corona" (PC) is the effect of such nanoprotein interactions. PC has a wide usage in pharmaceuticals, drug delivery, medicine, and industrial biotechnology.

A comprehensive computational study of amino acid interactions in membrane proteins.

Transmembrane proteins play a fundamental role in a wide series of biological processes but, despite their importance, they are less studied than globular proteins, essentially because their embedding in lipid membranes hampers their experimental characterization. In this paper, we improved our understanding of their structural stability through the development of new knowledge-based energy functions describing amino acid pair interactions that prevail in the transmembrane and extramembrane regions of membrane proteins. The comparison of these potentials and those derived from globular proteins yields an objective view of the relative strength of amino acid interactions in the different protein environments, and their role in protein stabilization.

DelPhi Suite: New Developments and Review of Functionalities.

Electrostatic potential, energies, and forces affect virtually any process in molecular biology, however, computing these quantities is a difficult task due to irregularly shaped macromolecules and the presence of water. Here, we report a new edition of the popular software package DelPhi along with describing its functionalities. The new DelPhi is a C++ object-oriented package supporting various levels of multiprocessing and memory distribution.

Structural Perspective on Revealing and Altering Molecular Functions of Genetic Variants Linked with Diseases.

Structural information of biological macromolecules is crucial and necessary to deliver predictions about the effects of mutations-whether polymorphic or deleterious (i.e., disease causing), wherein, thermodynamic parameters, namely, folding and binding free energies potentially serve as effective biomarkers.

DelPhiPKa: Including salt in the calculations and enabling polar residues to titrate.

DelPhiPKa is a widely used and unique approach to compute pK 's of ionizable groups that does not require molecular surface to be defined. Instead, it uses smooth Gaussian-based dielectric function to treat computational space via Poisson-Boltzmann equation (PBE). Here, we report an expansion of DelPhiPKa functionality to enable inclusion of salt in the modeling protocol.

Salt-bridge dynamics in intrinsically disordered proteins: A trade-off between electrostatic interactions and structural flexibility.

Intrinsically Disordered Proteins (IDPs) are enriched in charged and polar residues; and, therefore, electrostatic interactions play a predominant role in their dynamics. In order to remain multi-functional and exhibit their characteristic binding promiscuity, they need to retain considerable dynamic flexibility. At the same time, they also need to accommodate a large number of oppositely charged residues, which eventually lead to the formation of salt-bridges, imparting local rigidity.

CP: the complementarity plot for docking of proteins: implementing multi-dielectric continuum electrostatics.

The complementarity plot (CP) is an established validation tool for protein structures, applicable to both globular proteins (folding) as well as protein-protein complexes (binding). It computes the shape and electrostatic complementarities (S, E) for amino acid side-chains buried within the protein interior or interface and plots them in a two-dimensional plot having knowledge-based probabilistic quality estimates for the residues as well as for the whole structure. The current report essentially presents an upgraded version of the plot with the implementation of the advanced multi-dielectric functionality (as in Delphi version 6.

Nitric oxide sensing by chlorophyll a.

Nitric oxide (NO) acts as a signalling molecule that has direct and indirect regulatory roles in various functional processes in biology, though in plant kingdom its role is relatively unexplored. One reason for this is the fact that sensing of NO is always challenging. There are very few probes that can classify the different NO species.

Salt-bridge networks within globular and disordered proteins: characterizing trends for designable interactions.

There has been considerable debate about the contribution of salt bridges to the stabilization of protein folds, in spite of their participation in crucial protein functions. Salt bridges appear to contribute to the activity-stability trade-off within proteins by bringing high-entropy charged amino acids into close contacts during the course of their functions. The current study analyzes the modes of association of salt bridges (in terms of networks) within globular proteins and at protein-protein interfaces.

Proteus: a random forest classifier to predict disorder-to-order transitioning binding regions in intrinsically disordered proteins.

The focus of the computational structural biology community has taken a dramatic shift over the past one-and-a-half decades from the classical protein structure prediction problem to the possible understanding of intrinsically disordered proteins (IDP) or proteins containing regions of disorder (IDPR). The current interest lies in the unraveling of a disorder-to-order transitioning code embedded in the amino acid sequences of IDPs/IDPRs. Disordered proteins are characterized by an enormous amount of structural plasticity which makes them promiscuous in binding to different partners, multi-functional in cellular activity and atypical in folding energy landscapes resembling partially folded molten globules.

RNAHelix: computational modeling of nucleic acid structures with Watson-Crick and non-canonical base pairs.

Comprehensive analyses of structural features of non-canonical base pairs within a nucleic acid double helix are limited by the availability of a small number of three dimensional structures. Therefore, a procedure for model building of double helices containing any given nucleotide sequence and base pairing information, either canonical or non-canonical, is seriously needed. Here we describe a program RNAHelix, which is an updated version of our widely used software, NUCGEN.

DockQ: A Quality Measure for Protein-Protein Docking Models.

The state-of-the-art to assess the structural quality of docking models is currently based on three related yet independent quality measures: Fnat, LRMS, and iRMS as proposed and standardized by CAPRI. These quality measures quantify different aspects of the quality of a particular docking model and need to be viewed together to reveal the true quality, e.g.