Biochem Final: Hayden Lecture

what part of the mitochondria does hayden study?

inner mitochondrial membrane - cristae

what is the example of the disease that can cause damaged imm

barth’s syndrome

what is cardiolipin

-2 charge phospholipid that causes curvature in inner mitochondrial membrane

name of drug that treats barth’s syndrome + basic structure

SS-31 Peptide/Elamipretide
Tetrapeptide, charge of +3, two aromatic groups, two cationic groups

what does SS-31 do?

restores cristae structure within IMM → improved mitochondrial ATP production

how does SS-31 interact with the membrane

cationic groups engage with anionic phosphate groups
aromatic groups engage with hydrophobic lipid region

how does molecular dynamics work

builds a biological model of a membrane interacting with the molecule within a simulation box

all components in hayden’s molecular dynamics model

membrane with cardiolipin, drug, ions, and water within an enclosed simulation box

difference between phospholipids and cardiolipin

phospholipids → polar, neutral, 2 acyl chains
cardiolipin → anionic, -2 charge, 4 acyl chains

to show SS-31 crossing through the membrane and the affects of doing so, what does Hayden use?

Steered molecular dynamics → steer SS-31 through the membrane

how does hayden remove bias from steered molecular dynamics

umbrella sampling → simulates ss-31 at many points along the crossing pathway