Engineering gain-of-function mutants of a WW domain by dynamics and structural analysis.

Proteins gain optimal fitness such as foldability and function through evolutionary selection. However, classical studies have found that evolutionarily designed protein sequences alone cannot guarantee foldability, or at least not without considering local contacts associated with the initial folding steps. We previously showed that foldability and function can be restored by removing frustration in the folding energy landscape of a model WW domain protein, CC16, which was designed based on Statistical Coupling Analysis (SCA).

Design of novel cyanovirin-N variants by modulation of binding dynamics through distal mutations.

We develop integrated co-evolution and dynamic coupling (ICDC) approach to identify, mutate, and assess distal sites to modulate function. We validate the approach first by analyzing the existing mutational fitness data of TEM-1 β-lactamase and show that allosteric positions co-evolved and dynamically coupled with the active site significantly modulate function. We further apply ICDC approach to identify positions and their mutations that can modulate binding affinity in a lectin, cyanovirin-N (CV-N), that selectively binds to dimannose, and predict binding energies of its variants through Adaptive BP-Dock.

Toll-like receptor-4 299Gly allele is associated with Guillain-Barré syndrome in Bangladesh.

Objective: TLR4 plays an important role in the pathogenesis of Guillain-Barré syndrome (GBS). The relationships between polymorphisms and susceptibility to GBS are poorly understood. We investigated the frequency and assessed the association of two single nucleotide polymorphisms (SNPs) in the extracellular domain of (Asp299Gly and Thr399Ile) with disease susceptibility and the clinical features of GBS in a Bangladeshi cohort.

CD1A and CD1E gene polymorphisms are not associated with susceptibility to Guillain-Barré syndrome in the Bangladeshi population.

The post-infectious autoimmune polyradiculoneuropathy Guillain-Barré syndrome (GBS) is triggered by molecular mimicry between microbial glycolipid antigens and human peripheral nerve gangliosides. Single nucleotide polymorphisms in exon 2 of CD1A (*01/*02) and CD1E (*01/*02) were assessed using PCR-RFLP; no significant differences in genotype or allele frequency were observed between 200 patients with GBS and 200 healthy controls. CD1 gene polymorphisms cannot be recognized as a susceptibility or disease-causative factor for GBS in the Bangladeshi population.

Tumor necrosis factor-alpha -863C/A polymorphism is associated with Guillain-Barré syndrome in Bangladesh.

Guillain-Barré syndrome (GBS) is a post-infectious autoimmune polyneuropathy regulated by pro- and anti-inflammatory cytokines; TNFA polymorphisms may exert immune pathogenic roles in GBS. We assessed TNFA promoter region polymorphisms (-238G/A, -308G/A, -857C/T, -863C/A) in Bangladeshi patients with GBS (n=300) and healthy controls (n=300) by PCR-RFLP and ASO-PCR. TNFA -863CA was significantly associated with GBS disease susceptibility (P=0.

An endophytic Basidiomycete, Grammothele lineata, isolated from Corchorus olitorius, produces paclitaxel that shows cytotoxicity.

Grammothele lineata, an endophyte isolated in our laboratory from jute (Corchorus olitorius acc. 2015) was found to be a substantial paclitaxel producer. Taxol and its related compounds, produced by this endophyte were extracted by growing the fungus in simple nutrient media (potato dextrose broth, PDB).