ZymeCAD™ is a comprehensive platform for protein modeling and structure-guided protein engineering. ZymeCAD™ consists of a suite of proprietary algorithms that are used to:
Structural characteristics of the protein therapeutic and targets are studied in the context of energy (scoring) functions calibrated against empirically observed thermodynamic properties of the system. The detailed treatment of various dynamic and energetic aspects refines the realism of the system being modeled.
The ZymeCAD™ platform is designed to recognize hotspots and other critical characteristics of the protein therapeutic, driving the rational design of mutations.
Commercial software engineering practices, coupled with robust quality assurance standards and a world-class software engineering team have created an extensible, reliable and secure platform with efficient execution profiles on high performance computing resources.
High quality structural models of protein systems are a critical component in Zymeworks’ Protein Engineering Approach. Zymeworks’ Platform includes a number of proprietary tools used to build and refine the quality of models, incorporating structural data from multiple sources including homology and sequence data from related proteins, experimental binding information and mutational analysis such as alanine scanning.
Zymeworks’ Platform incorporates a number of proprietary deterministic and stochastic simulation approaches to sample changes within the target systems, including protein backbone, sidechain, and interdomain conformational changes. Proprietary simulation analysis results in the development of an understanding of the alternate conformational states of the protein of interest and its complexes vis-à-vis its mutants. This understanding is critical as many functionally important characteristics of proteins, including binding and stability, rely on the existence of an ensemble of structures in multiple conformational sub-states and transitions.
Zymeworks has developed and implemented proprietary energy and scoring functions that score and rank the stability of proteins and binding energies across protein interfaces. The functional form and parameters of the energy functions used by Zymeworks are calibrated against known experimental data and address a number of physically relevant interaction propensities of the protein and aspects of enthalpy, entropy and free energy. This empirical ranking is used in various protein engineering tasks including the analysis of Zymeworks Heterodimer Scaffolds.
Identifying a specific subset of key amino acids in a protein or protein system is critical to determining its functional characteristic and overall stability. These amino acid residues play a role either independently or as part of a cluster of networked residues, resulting in long-range effects of distal mutations. Zymeworks has developed proprietary algorithms that identify these critical residues (referred to as ‘hot spots’) based on characterization of residue properties in simulated trajectories of the protein. Additionally, Zymeworks has developed proprietary algorithms to quantify the mutability of specific residues based on its flexibility profile and local environment.