SOURSOP: A Python package for the analysis of simulations of intrinsically disordered proteins

Abstract

Conformational heterogeneity is a defining hallmark of intrinsically disordered proteins and protein regions (IDRs). The functions of IDRs and the emergent cellular phenotypes they control are associated with sequence-specific conformational ensembles. Simulations of conformational ensembles that are based on atomistic and coarse-grained models are routinely used to uncover the sequence-specific interactions that may contribute to IDR functions. These simulations are performed either independently or in conjunction with data from experiments. Functionally relevant features of IDRs can span a range of length scales. Extracting these features requires analysis routines that quantify a range of properties. Here, we describe a new analysis suite SOURSOP, an object-oriented and open-source toolkit designed for the analysis of simulated conformational ensembles of IDRs. SOURSOP implements several analysis routines motivated by principles in polymer physics, offering a unique collection of simple-to-use functions to characterize IDR ensembles. As an extendable framework, SOURSOP supports the development and implementation of new analysis routines that can be easily packaged and shared.

The Analytical Flory Random Coil Is a Simple-to-Use Reference Model for Unfolded and Disordered Proteins

“…The Journal of Physical Chemistry B analyzed as described previously, and all the all-atom trajectories can be obtained as described previously. 28 Specifically, all-atom simulations included both Monte Carlo and molecular dynamics simulations. Monte Carlo simulations include those of Ash1, 55 p53, 56 p27, 57 the notch intracellular domain, 58 and the hnRNPA1 low complexity domain.…”

Aberrant phase separation is a common killing strategy of positively charged peptides in biology and human disease

“…Protein structures for folded domains were taken from AlphaFold2 structure predictions 126 . The folded domain structures were analyzed to calculate the per-residue solvent- accessible surface area using SOURSOP and the 3D position of solvent-accessible residues were used to calculate 3D charge clustering (see above) 127 . Sparrow (https://github.com/idptools/sparrow) was used to calculate the sequence features for both IDRs and folded domains.…”

The analytical Flory random coil is a simple-to-use reference model for unfolded and disordered proteins

“…In comparing AFRC-derived polymeric properties with those obtained from all-atom simulations, we recapitulate sequence-to-ensemble features identified previously 25,28,67,69 . When comparing the normalized radii of gyration (R g Sim /R g AFRC ), we noticed the lower and upper bounds obtained here appear to be approximately 0.8 and 1.4, respectively.…”

“…However, we emphasize that there is massive variability observed on a per-sequence basis. In summary, while the presence of charged and proline residues clearly influences IDR dimensions, complex patterns of intramolecular interactions can further tune this behavior 2,17,28 . for the fraction of charged and proline residues vs. normalized radius of gyration is 0.58).…”

“…Depending on the experimental techniques employed, a variety of polymeric properties can be measured, including the radius of gyration (R g ), the hydrodynamic radius (R h ), the end-to-end distance (R e ), and the apparent scaling exponent (ν app ). These and many other parameters can be calculated directly from all-atom simulations, and the synergy of simulation and experiment has provided a powerful approach for constructing large ensembles of unfolded proteins for greater insight into the unfolded state 15,[18][19][20][21][22][23][24][25][26][27][28] .…”