PT  - JOURNAL ARTICLE
AU  - Vytautas Gapsys
AU  - Bert L. de Groot
TI  - Comment on ‘Response to comment on ‘Valid molecular dynamics simulations of human hemoglobin require a surprisingly large box size’’
AID  - 10.1101/812966
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 812966
4099  - http://biorxiv.org/content/early/2019/10/25/812966.short
4100  - http://biorxiv.org/content/early/2019/10/25/812966.full
AB  - We recently expressed three major concerns about a 2018 article of El Hage et al. about a claimed effect of the box size in molecular dynamics simulations of hemoglobin. In the response of the authors to our comment, none of these concerns have been addressed, yet the authors maintain their original conclusions. Here, we challenge those conclusions and provide additional data that reestablish our original concerns. In addition, we identified six additional flaws in the response from El Hage et al. as well as a number of technical concerns about the presented simulations and analyses. Taken together, we conclude that there is no basis to support the hypothesis of significant box size effects in MD simulations for the studied systems in the examined range.