ChemBioHTP/LassoHTP: LassoHTP: A High-Throughput Computational Tool for Lasso Peptide Structure Construction and Modeling

LassoHTP is a computational tool geared towards lasso peptide design and discovery. Major functionalities include the high throughput (HTP) construction of lasso peptides as well as HTP molecular dynamics (MD) simulations to predict lasso peptide thermodynamic parameters.

LassoHTP contains three main modules:1) Template constructor, 2) Template mutator, 3) High-throughput MD simulation. The template constructor module builds molecular templates, or scaffolds, of a lasso peptide with variable ring size, upper loop length, and tail length. The template mutator module mutates each of the residues on a given molecular template to fit a specified peptide sequence. Users can also randomly mutate the template as well as selectively mutate one or more topological sections of the template. The HTP MD simulation module performs multiscale-MD on LassoHTP-constructed lasso peptides. The module automates minimization, heating, and equilibration for each constructed lasso peptide as well as the curation of each MD stage's input file. The HTP component can also propogate multiple trajectories and in turn ensembles that can be used to calculate conformational entropies.