Computationally Designed Synthetic Peptides for Transporter Proteins Imparts Allostericity in Miltefosine Resistant Leishmania major.

Computationally Designed Synthetic Peptides for Transporter Proteins Imparts Allostericity in Miltefosine Resistant Leishmania major. Biochem J. 2020 May 11;: Authors: Kabra R, Ingale P, Singh S Abstract Emergence of drug resistance is major concern for combating against Cutaneous Leishmaniasis, a neglected tropical disease affecting 98 countries including India. Miltefosine is the only oral drug available for the disease and Miltefosine transporter proteins play pivotal role in the emergence of drug resistant Leishmania major. The cause of resistance is less accumulation of drug inside the parasite either by less uptake of drug due to decrease in the activity of P4ATPase-CDC50 complex or by increased efflux of the drug by P-glycoprotein (P-gp, an ABC transporter). In this paper, we are trying to allosterically modulate the behavior of resistant parasite (L. major) towards its sensitivity for the existing drug (Miltefosine, a phosphatidylcholine analog). We have used computational approaches to deal with the conservedness of the proteins and apparently its 3D structure prediction through ab initio modeling. Long scale membrane embedded molecular dynamics simulations were carried out to study the structural interaction and stability. Parasite specific motifs of these proteins were identified based on machine learning technique, against which a peptide library was designed. The protein-peptide docking shows good binding energy of pepti...
Source: The Biochemical Journal - Category: Biochemistry Authors: Tags: Biochem J Source Type: research