For all analyses of MD simulations, amino acid pocket scores were evaluated for the last 30 ns of the trajectories to ensure structural equilibration.

PC190723 binds a cleft beneath the H7 helix and adjacent to the T7 loop of FtsZ, as demonstrated in an amino acid residues that are within 6 A of PC190723, including G193, G196, and N263, which induce drug resistance when mutated in SaFtsZ.

In this study, we define the “ideal” PC190723-binding pocket as the microenVironment of the 20 amino acid residues Within 6 A of the PC190723 molecule in an SaFtsZ-PC190723 co-crystal structure (PDB ID: 4DXD) [17].

For comparison With other crystal structures, we defined the PC197023-binding pocket as the equivalent amino acids after a structural alignment (Fig.

Thus, small fluctuations in the amino acid functional centers within the pocket can perturb the local physiochemical properties calculated for each residue, pointing to the subtle structural balance required for the most optimal drug-binding environment that can be extremely sensitive to thermal fluctuations.

Interestingly, these residues correspond to amino acids Within the T7 loop, a highly conserved structural element near the site of monomer association that plays an important role in GTP hydrolysis [19].

Blue, strictly conserved amino acids; red, highly conserved amino acids (75% conservation).

The other two samples had mutations in the HEAT 5—9 repeats but outside of the apparent ~10 amino acid mutational hotspots

These results show that cryptic 3’SS selection only occurs in tumors carrying mutations in one of the five ~10 amino acid hotspots in the HEAT 5—9 repeats and is not limited to cancers in Which SF3BI is recurrently mutated.

We found that cryptic 3’SS selection is limited to tumors with mutations in the five ~10 amino acid hotspots in the SF3BI HEAT 5—9 repeats and that these mutations are associated with cryptic 3’SS selection across different cancer types and even in cancers in which SF3BI is not recurrently mutated.

Our analysis of tumors with SF3BI mutations shows that cryptic 3’SS selection occurs only in samples with missense mutations at ~10 amino acid hotspots in the fifth to ninth HEAT repeats.

Amino acid sequences corresponding to the mutated protein isoforms were also available from the COSMIC database.

In other words, a domain instance refers to a specific amino acid subsequence within a given single protein that matches to a given domain type.

It has been proposed that oncoproteins tend to be recurrently mutated at the same amino acid residues, while tumor suppressor proteins tend to be mutated throughout their length[15].

The p53 protein structure is colored according to amino acid chain.