The exact calculations required to convert bond lengths and angles into 3D atom coordinates are given in the supporting text of Tien et al. Once we have determined the desired geometry, we have to calculate the actual position of all atoms in 3-space and then add the atoms to the structure object. In practice, we will usually want to specify the dihedral backbone angles ϕ and ψ, and possibly the rotamers, whereas all other bond lengths and angles should be set to reasonable defaults for the amino acid under consideration. This means we have to determine all bond lengths and angles. First, we have to establish the desired geometric arrangement of all atoms in the residue to be added. The seemless integration with Biopython’s PDB module means that we can leverage a wide range of existing functionality, such as writing structures to PDB files or measuring distances between atoms.Īdding a residue to an existing polypeptide chain involves two separate steps. The generated models are stored as structure objects using the PDB module of Biopython ( Bio.PDB, Hamelryck & Manderick 2003). In combination, these two functions enable the construction of arbitrary polypeptide chains. Our library also allows a user to generate an individual amino acid residue and place it into an otherwise empty model. The key function our library provides is to add a residue at the C terminus of an existing polypeptide model, using arbitrary backbone angles. The entire PeptideBuilder package is also available online at. Both files are provided as Supplemental Information 1. The library consists of two Python files comprising a total of approximately 2000 lines of code. This effort resulted in the Python library PeptideBuilder, which we describe here. Specifically, many tools suitable for computational biology and bioinformatics are available ( Cock et al., 2009), including tools to read, manipulate, and write PDB (Protein Data Bank) files ( Hamelryck & Manderick, 2003). We decided to write this library in the language Python ( Python Sofware Foundation, 2013), as this language is widely used in scientific computing. After review of the available software packages, we determined that there was a need for a lightweight library, implemented in a modern programming language, that would allow us to construct arbitrary peptides in any desired conformation. However, Ribosome is implemented in Fortran, an outdated programming language that integrates poorly with modern bioinformatics pipelines.įor a recent analysis by our group, we wanted to systematically enumerate GLY-X-GLY tripeptides in all allowed conformations ( Tien et al., 2012). Finally, the Rose lab has developed Ribosome ( Srinivasan, 2013), a small program with the express purpose of creating model peptides. One can also construct peptides manually in some graphical molecular modeling packages, such as Swiss-PdbViewer ( Guex & Peitsch, 1997). It is possible to perform this task in PyRosetta ( Chaudhury, Lyskov & Gray, 2010 Gray et al., 2013), but that approach incurs the overhead of the entire Rosetta protein modeling package ( Leaver-Fay et al., 2011). In comparison, a relatively simple task, the ab-initio creation of a protein structure in a desired conformation, has received little attention. Examples include visualization ( Schrödinger, 2013), mutagenesis ( Schrödinger, 2013 Leaver-Fay et al., 2011), high-throughput computational analysis ( Hamelryck & Manderick, 2003 Grant et al., 2006), ab-initio protein folding and protein design ( Leaver-Fay et al., 2011), and homology modeling and threading ( Eswar et al., 2006 Zhang, 2008). To aid this work, many different software tools have been developed. Researchers working in structural biology and related fields frequently have to create, manipulate, or analyze protein crystal structures.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |