The Maranas group is 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 targeted 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.

Reconstruction, Analysis & Redesign of Metabolic Pathways

Reconstruction, Analysis & Redesign of Metabolic Pathways

  • Development of kinetic models of metabolism
  • Computational procedures for strain optimization using kinetic models of metabolism
  • Metabolic modeling of photosynthetic cyanobacteria, anaerobic organisms (clostridia & archaea) and plants(maize)
  • Metabolic modeling of microbial communities
  • Metabolic flux elucidation using MFA at a genome-scale
  • Generation of a metabolites and reaction knowledgebase (MetRxn)
  • Genome-scale gene/reaction essentiality and synthetic lethality analysis
  • Computational procedures for strain optimization using stoichiometric models of metabolism
  • Analysis of network properties of Metabolic Models

Learn more
Computational Protein Design

Computational Protein Design

  • Structure-Based Computational Enzyme Design
  • De novo computational antibody design
  • Enzyme design with improved catalytic properties
  • 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

Learn more