ProteinShop: A tool for interactive protein manipulation and steering

Abstract

We describe ProteinShop, a new visualization tool that streamlines and simplifies the process of determining optimal protein folds. ProteinShop may be used at different stages of a protein structure prediction process.First, it can create protein configurations containing secondary structures specified by the user. Second, it can interactively manipulate protein fragments to achieve desired folds by adjusting the dihedral angles of selected coil regions using an Inverse Kinematics method. Last, it serves as a visual framework to monitor and steer a protein structure prediction process that may be running on a remote machine. ProteinShop was used to create initial configurations for a protein structure prediction method developed by a team that competed in CASP5. ProteinShop's use accelerated the process of generating initial configurations, reducing the time required from days to hours. This paper describes the structure of ProteinShop and discusses its main features.

Mechanism of copper(II)-induced misfolding of Parkinson's disease protein

“…Unfortunately, due to the large time scales involved, the formation of β -sheets in full-length proteins cannot be studied in atomistic simulations at present. Instead, we develop multiple plausible candidates for a β -sheet located in the area where alignment is observed, using inverse kinematics28 and testing their dynamic stabilities in extended MD simulations. Among all the candidate structures, only one turns out to be stable during the MD simulations.…”

“…The exploration of possible β -sheet registrations is aided by inverse kinematics as implemented within ProteinShop28 and based on the AMBER41 force field. By using inverse kinematics we are able to reduce the sample set to contain only energetically favorable β -sheet conformations.…”

Repurposing citizen science games as software tools for professional scientists

“…Foldit— and thus Foldit Standalone—has been optimized for allowing the user to modulate the shape and composition of a protein’s structure within the Rosetta energy function, either for predicting its naturally occurring structure or engineering a novel one. Though other software has been developed for protein structure manipulation (including ProteinShop [10] and Sculpt [43]), Foldit was designed with novice users at the forefront, and to provide an interface to the protein modeling features of the Rosetta software. Foldit’s primary coloring scheme, for example, is based on the per-residue energy of the protein.…”

A dynamic data structure for flexible molecular maintenance and informatics

“…DPG has potential applications in interactive software tools developed for de novo drug design (e.g., [30,46,18,29]), protein folding (e.g., [28,14]) and molecular docking (e.g., [33,2]) that use human intuition and biological knowledge in order to steer the prediction process. These applications often need to handle extremely large molecules and macromolecules (e.g., as shown in Figure 1 Rice Dwarf Virus with 3.5 million atoms, and Microtubule has 1.2 million), and need to perform a sequence of dynamic updates on them in real time.…”

“…In a series of interactive steps it applies a set of problem-specific mutation (e.g., add/remove atom, add/remove group) and recombination operators on a set of evolving molecules, and keeps track of several chemical and biological properties of each molecule (e.g., molecular mass, hydrophobicity, etc.). The ProteinShop software [28,14] allows the interactive creation of protein structures (e.g., through shape manipulation) given an amino acid sequence and a sequence of predicted secondary structure types for each amino acid. DockingShop [33] is a successor of ProteinShop, which provides an interactive docking environment with flexibility of side chains and backbone movement.…”