Protein engineering is a fairly new field, increasing exponentially within the last 20 years, with the advent of molecular dynamics simulations(MD). By manipulating the amino acid sequence of known proteins, we can develop new proteins with radically different functions. We will work with the enzyme, dihydrofolate reductase (DHFR), which is the first committed step of nucleic acid biosynthesis. The goal of our research is to modify the cofactor pocket of DHFR, which naturally binds NADP, and re-engineer the pocket to accept a different cofactor, NAD. We will use MD softwares (Amber and Rosetta) to determine the residues that are most critical in binding NADP. This will allow us to predict what amino acids substitutions to make in the mutant DHFR. MD trajectories of the mutants can be compared to native DHFR to see the effect of those mutations in the 3-D structure. MD can also numerically verify the success of mutations through root-mean square deviation (RMSD) calculations . Graphic verification will be done by using Pymol and VMD. Computational docking will be done using the Amber module, Autodock, to ensure that NADH fits into both the active site and substrate pocket of any successful mutant. Ultimately, we will generate the DNA sequence of the successful mDHFR for wet lab verification. Our goal is to find an amino acid substitutions that when simulated has the same structure and function as the native DHFR but preferentially binds to NAD, not NADP.