Biology subjects

Maity, H.

Publications and source records attributed to Maity, H..

5 recordsLinked to original sources

bioRxiv2025

Sequence Complexity Dictates Polymer Mixing

Polymer association in confined spaces governs diverse phenomena from protein aggregation to DNA condensation. We investigate the sequence-level mechanisms underlying this behavior through exact enumeration of two confined AB-type block copolymers on a two-dimensional lattice, revealing how sequence complexity controls mixing against de-mixing. We reveal that sequence complexity (heterogeneity), quantified by Shannon entropy H2, acts as a determinant between self-folded low-mixed state and high-mixed state. High-complexity sequences (H2 = 1.86 bits) with short-length repeats achieve near-complete inter-chain overlap through cooperative chain collapse, while low-complexity blocky sequences (H2 = 1.26 bits) maintain extended conformations with less overlapping. Free energy analysis reveals a steep increase in mixing barriers for low-complexity compared to surmountable barrier for high-complexity sequences. We find that geometric confinement modulates but does not override these sequence-dependent behaviors, with asymmetric confinement enhancing heterogeneity in overlapping for both sequence type (pronounced in high-H2 sequences). Our theory could be applicable in assessing the phase behavior of repeat protein and nucleic acid sequences.

biophysics↗

bioRxiv2023

Odd-even disparity in the population of slipped hairpins in RNA repeat sequences with implications for phase separation

Low complexity nucleotide repeat sequences, which are implicated in several neurological disorders, undergo liquid-liquid phase separation (LLPS) provided the number of repeat units, n, exceeds a critical value. Here, we establish a link between the folding landscapes of the monomers of trinucleotide repeats and their propensity to self-associate. Simulations using a coarse-grained Self-Organized Polymer (SOP) model for (CAG)n repeats in monovalent salt solutions reproduce experimentally measured melting temperatures, which are available only for small n. By extending the simulations to large n, we show that the free energy gap, {Delta}GS, between the ground state (GS) and slipped hairpin (SH) states is a predictor of aggregation propensity. The GS for even n is a perfect hairpin (PH) whereas it is a SH when n is odd. The value of {Delta}GS (zero for odd n) is larger for even n than for odd n. As a result, the rate of dimer formation is slower in (CAG)30 relative to (CAG)31, thus linking {Delta}GS to RNA-RNA association. The yield of the dimer decreases dramatically, compared to the wild type, in mutant sequences in which the population of the SH is decreases substantially. Association between RNA chains is preceded by a transition to the SH even if the GS is a PH. The finding that the excitation spectra, which depends on the exact sequence, n, and ionic conditions, is a predictor of self-association, should also hold for other RNAs (mRNA for example) that undergo LLPS.

biophysics↗

bioRxiv2022

Salt Induced Transitions in the Conformational Ensembles of Intrinsically Disordered Proteins

Salts modulate the behavior of intrinsically disordered proteins (IDPs). In low ionic strength solutions, IDP conformations are primarily perturbed by the screening of electrostatic interactions, independent of the identity of the salt. In this regime, insight into the IDP behavior can be obtained using the theory for salt-induced transitions in charged polymers. However, in high ionic strength solutions, salt-specific interactions with the charged and uncharged residues, known as the Hofmeister effect, influence IDP behavior. There is a lack of reliable theoretical models in high salt concentration regimes to predict the salt effect on IDPs. Using a coarse-grained simulation model for the IDPs and experimentally measured water to salt solution transfer free-energies of various chemical groups, we studied the salt-specific transitions induced in the IDPs conformational ensemble. We probed the effect of three different salts, ranging from protective osmolyte to denaturant, on five IDPs belonging to various polymer classes classified based on charge content. The transitions observed in the IDP conformational ensembles are dependent on the salt used and the IDP polymer class. An important implication of these results is that a suitable salt can be identified to induce condensation of an IDP through liquid-liquid phase separation.

biophysics↗

bioRxiv2020

A preliminary ecological profile of Kyasanur Forest disease virus hosts among the mammalian wildlife of the Western Ghats, India

Kyasanur Forest disease (KFD) is one of Indias severe arboviruses capable of causing prolonged debilitating disease. It has been expanding beyond its historical endemic locus at an alarming rate over the last two decades. The natural nidus of this zoonosis is located in the monsoon rainforest of the Western Ghats, India, which is one of the worlds most important biodiversity hotspots. Definitive reservoir hosts for KFD virus (KFDV) have yet to be delineated, and thus much of the infection ecology of this virus, and its consequent transmission dynamics, remains uncertain. Given its unique biogeographical context, identifying ecological parameters of KFDV relevant to the virus epidemiology has been complex and challenging. The challenge has been exacerbated by diminished research efforts in wildlife surveillance over the last two decades, coinciding with the expansion of the range of KFD across the region. The current investigation sought to define a preliminary ecological profile of KFDV hosts based on their life history and feeding traits to aid in re-establishing targeted wildlife surveillance and to discern those ecological traits of wildlife hosts that may improve our understanding of KFD epidemiology. The importance of fast-living among KFDV hosts was of special interest with respect to the latter aim. We compared mammalian traits between host and non-host species using general additive models and phylogenetic generalised linear models. This study found that both body mass and forest forage were strongly associated with mammalian host infection status, but that reproductive life history traits were not. These findings will help in structuring ecologically based wildlife surveillance and field investigations, while also helping to parameterise novel epidemiological models of zoonotic infection risk that incorporate species functional traits in a region where biogeography, landscape ecology, and community ecology manifest extraordinary complexity, particularly under growing anthropogenic pressure.

ecology↗

bioRxiv2018

Universal nature of collapsibility in the context of protein folding and evolution

Theory and simulations predicted sometime ago that the sizes of unfolded states of globular proteins should decrease continuously as the denaturant concentration is shifted from a high to a low value. However, small angle X-ray scattering (SAXS) data were used to assert the opposite, while interpretation of single molecule Forster resonance energy transfer experiments (FRET) supported the theoretical predictions. The disagreement between the two experiments is the SAXS-FRET controversy. By harnessing recent advances in SAXS and FRET experiments and setting these findings in the context of a general theory and simulations, we establish that compaction of unfolded states is universal. The theory also predicts that proteins rich in {beta}-sheets are more collapsible than -helical proteins. Because the extent of compaction is small, experiments have to be accurate and their interpretations should be as model free as possible. Theory also suggests that collapsibility itself could be a physical restriction on the evolution of foldable sequences, and provides a physical basis for the origin of multi-domain proteins.

biophysics↗