The open-source Masala software suite: Facilitating rapid methods development for synthetic heteropolymer design

Area of Science:

• Computational Biology
• Biophysics
• Software Engineering

Background:

• Canonical protein design leverages machine learning, but synthetic heteropolymer design primarily uses physics-based methods.
• The Rosetta software is a key tool for physics-based design, but its architecture presents limitations for new method development.
• Existing software architecture hinders innovation due to its aging, monolithic, non-open-source nature and steep learning curve.

Purpose of the Study:

• Introduce Masala, a free, open-source C++ software suite designed to extend and potentially succeed Rosetta.
• Develop a modular software architecture for modern computing hardware to facilitate new methods development in heteropolymer design.
• Implement efficient modules for accelerating protein and synthetic peptide design, including drop-in replacements for Rosetta's core functions.

Main Methods:

• Developed Masala as a set of C++ libraries with a modular architecture and automated API layer creation.
• Implemented plugin modules for Masala that can be compiled independently and loaded at runtime.
• Integrated Masala's real-valued local optimizers and cost function network optimizers as replacements for Rosetta's minimizer and packer.

Main Results:

• Masala's modular design allows for easy addition of new functionalities by novice developers without altering existing source code.
• Masala modules provide significant speedups, up to two orders of magnitude, for tasks like protein and synthetic peptide design.
• Implemented design-centric guidance terms in Masala for promoting desirable features (e.g., hydrogen bond networks) and discouraging undesirable ones (e.g., unsatisfied buried hydrogen bond donors/acceptors).

Conclusions:

• Masala offers a flexible, efficient, and open-source alternative for heteropolymer design, addressing limitations of existing software.
• The software's architecture facilitates rapid development and integration of new design methods, accelerating scientific discovery.
• Future development will focus on expanding Masala's capabilities to further advance protein and synthetic polymer design.