Biology subjects

Bashar, M. A.

Publications and source records attributed to Bashar, M. A..

3 recordsLinked to original sources

bioRxiv2025

Unraveling the distinct motion bias of TrkA-NGF complex in NGFR100W-driven HSAN V disease

Nerve growth factor (NGF), which binds to tropomyosin-related kinase A (TrkA) receptor, plays essential roles in neuronal survival and function and is also a potent mediator of pain sensation. Mutations in NGF, particularly NGFR100W, cause hereditary sensory autonomic neuropathy V (HSAN V), which is characterized by insensitivity to pain but without impairment of neurotrophin function. Even though several studies reported the mechanism of growing HSAN V disease, the dynamic mechanisms that dictate its functional specificity remain unclear. In this study, we performed a microsecond scale molecular dynamics (MD) simulation to elucidate the changes in the structural dynamics of NGF by NGFR100W at an atomic level to dissect the distinct motion bias for specific TrkA functions. We found that the NGFR100W reduced NGF dimerization while its binding to the TrkA remained unchanged. NGFR100W enhanced the magnitude of bond formation in the different regions from TrkA, which induced different correlated and dynamic motions associated with impaired nociceptive signaling. The dynamics scenario from this study, shedding light on the deleterious role of NGFR100W, provides new structural insights into the function-oriented dynamics motion of the TrkA-NGF complex, offering potential avenues for designing new therapeutics.

neuroscience↗

bioRxiv2024

Elucidating conformational alteration of human islet amyloid polypeptide by nonsynonymous substitution

Islet amyloid polypeptide (IAPP) is a peptide hormone that serves multiple essential functions, including metabolism and regulating gastric emptying and satiation through amylin receptors. However, mutations in the IAPP, notably in the amyloidogenic segment (20-29 amino acid residues), cause its aggregation and amyloid formation, which leads to {beta}-cell toxicity and death in type 2 diabetes mellitus (T2DM) and protein misfolding disorders (PMDs). The current work aims to elucidate the non-synonymous variants in the IAPP, which may adversely affect its function and rise to T2DM and PMDs. We harnessed in silico non-synonymous single-nucleotide polymorphisms (nsSNPs) assessment and molecular dynamics (MD) simulation to discover the potential deleterious mutants that cause T2DM and PMDs. Firstly, we executed nsSNPs prediction in IAPP using the NCBI dbSNP server, and then, all the predicted nsSNPs were assessed by a total of 26 in silico tools to find out which possessed the most deleterious effect in IAPP. Finally, MD simulation was carried out utilizing the most deleterious nsSNPs to check which significantly alters the conformational dynamics of IAPP. We found a total of 62 nsSNPs, among which the top 4 deleterious nsSNPs (T37P, L45P, G66R, and T69I) were selected based on the deleteriousness predictions by in silico tools and their location in the mature IAPP sequence (34-70 amino acid residues). MD simulations further confirm that three variants (T37P, L45P, and G66R) significantly alter the conformational dynamics of IAPP, suggesting a potential starting point for future research to elucidate the roles of these variants in IAPP aggregation and amyloid formation and their associations with T2DM and PMDs.

biophysics↗

bioRxiv2018

Age analysis and growth patterns of Tenualosa ilisha using otolith examination and length-weight relationships from different regions of Bangladesh

The assessment of age and growth patterns provides crucial information on numerous aspects of the population dynamics in fish, which can, in turn, be used to determine a sustainable fishing rate and inform effective resource management practices. However, studies on the age and growth pattern of Tenualosa ilisha (commonly referred to as hilsa) are plagued by a lack of essential information; addressing this data gap is the aim of the present study. Six diverse habitats across Bangladesh were chosen as sampling sites for hilsa collection. For age determinations, the lunar rings in the otolith of the hilsa fish that are periodically-deposited in accordance with the lunar cycle were used to reflect 14-day increments of time. The length and weight of each fish were recorded prior to otolith extraction. The resulting otoliths were polished to enable the visualization and quantification of their lunar rings with a high-magnification microscope. Except for the Kali River and Gaglajur Haor samples, the age of the fish correlated strongly with both their length and weight (r > 0.95; p < 0.05). Again, aside from those from the Kali River and Gaglajur Haor, all of the samples exhibited positive allometric growth patterns (b > 3) with the fish from the Tetulia River being the most positive (b = 3.48). The causes these variations are not yet clearly understood, however; the nutrient availability, environmental variation, and genetic-environmental interactions are likely contributors to the diversities displayed by the hilsa from different regions of Bangladesh.

molecular biology↗