The C. Maranas Chemical & Biological Systems Optimization Laboratory at PSU is currently working on the development of algorithmic and, in particular, optimization techniques to support the analysis and redesign of biological systems at different scales.
At the protein level, we are interested in computationally inferring what amino acid compositions are likely to yield i) proteins or antibodies with targedted binding affinities and ii) enzymes with improved stability, specificity and activity for specific biotransformations. To this end, we make use of ab initio energy calculations at the ground and transition states, MD simulations, as well as scoring functions based on bioinformatics inspired analyses.
At the metabolic network level, we are pursuing methods for automating the generation, curation, and correction of genome-scale models of metabolism. We are also interested in generating isotope mapping models to support metabolic flux elucidation using MFA. In addition, we are working towards developing computational tools to help decide how to engineer (i.e., through gene knock-in/out/up/down(s)) biological production systems.
A unifying feature of these seemingly disjoint research targets is the need to systematically search through many network configurations, amino acid compositions, protein structures, etc. and identify the "best" one. To this end, the development of efficient theoretical, algorithmic, and computational techniques for arriving at relevant as well as theoretically sound results while maximizing computational efficiency is pursued.
Computational Protein Design
Designing Novel Antibody Binding Pockets
Development of a Computational QM/MM Protocol for Enzyme Redesign
Altering Enzyme Cofactor Specificity
A Computational Procedure for Transferring a Binding Site Onto an Existing Protein Scaffold
An Iterative Computational Protein Library Redesign and Optimization Procedure
Protein Library Design Using Scoring Functions or Clash Maps
Modeling and Optimization of Directed Evolution Protocols
Reconstruction, Analysis, & Redesign of Metabolic Pathways
Genome-scale Gene/Reaction Essentiality and Synthetic Lethality Analysis
Elucidation of Metabolic Fluxes using Labeled Isotopes
Reconstruction of Genome-Scale Metabolic Models
Curation of Genome-Scale Metabolic Models
Computational Procedures for Strain Optimization Using Stoichiometric Models of Metabolism
Analysis of Network Properties of Metabolic Models
Analysis and Redesign for Kinetic Models of Metabolism
Signaling Networks and Tumor Modeling
Development of Multiscale Models of Tumor Progression
Analysis and Redesign of Signaling Networks
Synthetic Circuits and Regulatory Networks
Design of Synthetic Circuits
Hierarchical Methods for Regulatory Network Inference
Optimal Decision Making in Product & Process Planning
Design and Scheduling Real Options based Planning
Supply Chain Planning and CPI Design and Scheduling