How You Know You're in Love: Epigenetics, Stress & Gender Identity
Karissa Sanbonmatsu | TEDxABQ
Alert: Interested in going for a competitive post-doctoral fellowship with NIH or LANL about ribosome simulation, RNA secondary structure bioinformatics or lncRNA biochemistry? Please email Karissa at firstname.lastname@example.org
The Sanbonmatsu team uses computational and experimental approaches to understand the mechanism of a diverse array of non-coding RNA systems, including ribosomes, riboswitches and long non-coding RNAs. Originally focusing on large-scale simulations of the ribosome, we have expanded into joint computational/experimental studies of riboswitches and purely experimental studies of long non-coding RNAs. The ribosome is one of the few large RNA systems that has been studied mechanistically. We are applying our knowledge gained from ribosome studies to long non-coding RNA systems.
We are performing large-scale molecular simulations of the ribosome to uncover the energy landscape of tRNA selection and translocation. We are using explicit solvent, reduced-model and enhanced sampling methods.
LncRNAs (typically 1-10 kB) play key roles in development and disease and are often involved in epigenetic mechanism. We are using experimental biochemistry appoaches to probe the structure of long non-coding RNAs (lncRNAs).
Riboswitches use competing secondary structures to control gene expression. We are using an integrated experiment/computation approach to understand the role of ligand binding, magnesium and the expression platform in controlling riboswitch conformation.
Tatyana V Budkevich, Jan Giesebrecht, Elmar Behrmann, Justus Loerke, David JF Ramrath, Thorsten Mielke, Jochen Ismer, Peter W Hildebrand, Chang-Shung Tung, Knud H Nierhaus, Karissa Y Sanbonmatsu, Christian MT Spahn
Cell 158 (1), 121-131, 2014
The extent to which bacterial ribosomes and the significantly larger eukaryotic ribosomes share the same mechanisms of ribosomal elongation is unknown. Here, we present subnanometer resolution cryoelectron microscopy maps of the mammalian 80S ribosome in the posttranslocational state and in complex with the eukaryotic eEF1A⋅ Val-tRNA⋅ GMPPNP ternary complex, revealing significant differences in the elongation mechanism between bacteria and mammals. Surprisingly, and in contrast to bacterial ... .
KY Sanbonmatsu Journal of molecular biology 426 (19), 3197-3200, 2014
The ribosome is responsible for implementing the genetic code by reading instructions encoded in mRNA and manufacturing the corresponding protein ,  and . The suite of tRNAs act as a molecular look-up table, converting the 4-letter alphabet of nucleic acids to the 20-letter alphabet of proteins. Reading the mRNA similar to a ticker tape, for each 3-nucleotide codon, the ribosome must select the tRNA carrying the corresponding amino acid and reject all other tRNAs. This is a difficult task, as the ribosome is immersed in a sea of incorrect ...
Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms, 2014
Riboswitch RNAs play key roles in bacterial metabolism and represent a promising new class of antibiotic targets for treatment of infectious disease. While many studies of riboswitches have been performed, the exact mechanism of riboswitch operation is still not fully understood at the atomistic level of detail. Molecular dynamics simulations are useful for interpreting existing experimental data and producing predictions for new experiments. Here, a wide range of computational studies on riboswitches is reviewed. By elucidating ...
Prem S Kaushal, Manjuli R Sharma, Timothy M Booth, Emdadul M Haque, Chang-Shung Tung, Karissa Y Sanbonmatsu, Linda L Spremulli, Rajendra K Agrawal
Proceedings of the National Academy of Sciences 111 (20), 7284-7289, 2014
The mammalian mitochondrial ribosomes (mitoribosomes) are responsible for synthesizing 13 membrane proteins that form essential components of the complexes involved in oxidative phosphorylation or ATP generation for the eukaryotic cell. The mammalian 55S mitoribosome contains significantly smaller rRNAs and a large mass of mitochondrial ribosomal proteins (MRPs), including large mito-specific amino acid extensions and insertions in MRPs that are homologous to bacterial ribosomal proteins ...
SRyan L Hayes, Jeffrey K Noel, Paul C Whitford, Udayan Mohanty, Karissa Y Sanbonmatsu, José N Onuchic
Biophysical journal 106 (7), 1508-1519, 2014
The stability of RNA tertiary structures depends heavily on Mg2+. The Mg2+-RNA interaction free energy that stabilizes an RNA structure can be computed experimentally through fluorescence-based assays that measure Γ2+, the number of excess Mg2+ associated with an RNA molecule. Previous explicit-solvent simulations predict that the majority of excess Mg2+ ions interact closely and strongly with the RNA, unlike monovalent ions such as K+, suggesting that an explicit treatment of Mg2+ is important for capturing ...