MOESM1 of Homology modelling, molecular docking, and molecular dynamics simulations reveal the inhibition of Leishmania donovani dihydrofolate reductase-thymidylate synthase enzyme by Withaferin-A

Additional file 1: Figure S1. The structures of ligands: (A) Withaferin-A, (B) Methotrexate, (C) DHFA drawn using Chemdraw ultra version 12.0 software. Figure S2. Sequence identity between Hu DHFR and Ld DHFR-TS. Asterisks indicate identical amino acids. Dots and colons indicate conserved amino acid substitutions. Dashes indicate gaps. Figure S3. Sequence identity between Hu TS and Ld DHFR-TS. Asterisks indicate identical amino acids. Dots and colons indicate conserved amino acid substitutions. Dashes indicate gaps. Figure S4. Sequence identity between Ld DHFR-TS and T.cruzichain A. Asterisks indicate identical amino acids. Dots and colons indicate conserved amino acid substitutions. Dashes indicate gaps. Figure S5. Ramachandran Plot: (A) Modelled Ld DHFR-TS and (B) reference T. cruzi DHFR-TS obtained using PROCHECK. Figure S6. Local quality estimate of (A) modelled Ld DHFR-TS and (B) reference T.cruzi DHFR-TS obtained from Swiss model. Figure S7. Secondary structures of (A) modelled Ld DHFR-TS and (B) reference T.cruzi DHFR-TS obtained from PDB sum. Table S1. Features of the generated Ld DHFR-TS model from Swiss model. Table S2. Ramachandran plot Statistics from PROCHECK results for modelled Ld DHFR-TS protein and reference T. cruzi DHFR-TS protein. Table S3. Drug likeness properties of WA from molsoft

Advances in Animal Models and Cutting-Edge Research in Alternatives: Proceedings of the Third International Conference on 3Rs Research and Progress, Vishakhapatnam, 2022.

Animal experimentation has been integral to drug discovery and development and safety assessment for many years, since it provides insights into the mechanisms of drug efficacy and toxicity (e.g. pharmacology, pharmacokinetics and pharmacodynamics). However, due to species differences in physiology, metabolism and sensitivity to drugs, the animal models can often fail to replicate the effects of drugs and chemicals in human patients, workers and consumers. Researchers across the globe are increasingly applying the Three Rs principles by employing innovative methods in research and testing. The Three Rs concept focuses on: the replacement of animal models (e.g. with in vitro and in silico models or human studies), on the reduction of the number of animals required to achieve research objectives, and on the refinement of existing experimental practices (e.g. eliminating distress and enhancing animal wellbeing). For the last two years, Oncoseek Bio-Acasta Health, a 3-D cell culture-based cutting-edge translational biotechnology company, has organised an annual International Conference on 3Rs Research and Progress. This series of global conferences aims to bring together researchers with diverse expertise and interests, and provides a platform where they can share and discuss their research to promote practices according to the Three Rs principles. In November 2022, the 3rd international conference, Advances in Animal Models and Cutting-Edge Research in Al- ternatives, took place at the GITAM University in Vishakhapatnam (AP, India) in a hybrid format (i.e. online and in- person). These conference proceedings provide details of the presentations, which were categorised under five different topic sessions. It also describes a special interactive session on in silico strategies for preclinical research in oncology, which was held at the end of the first day